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1
Arregui, Carlos, Purnima Pathre, Jack Lilien, and Janne Balsamo. "The Nonreceptor Tyrosine Kinase Fer Mediates Cross-Talk between N-Cadherin and β1-Integrins." Journal of Cell Biology 149, no. 6 (June 12, 2000): 1263–74. http://dx.doi.org/10.1083/jcb.149.6.1263.
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Cadherins and integrins must function in a coordinated manner to effectively mediate the cellular interactions essential for development. We hypothesized that exchange of proteins associated with their cytoplasmic domains may play a role in coordinating function. To test this idea, we used Trojan peptides to introduce into cells and tissues peptide sequences designed to compete for the interaction of specific effectors with the cytoplasmic domain of N-cadherin, and assayed their effect on cadherin- and integrin-mediated adhesion and neurite outgrowth. We show that a peptide mimicking the juxtamembrane (JMP) region of the cytoplasmic domain of N-cadherin results in inhibition of N-cadherin and β1-integrin function. The effect of JMP on β1-integrin function depends on the expression of N-cadherin and is independent of transcription or translation. Treatment of cells with JMP results in the release of the nonreceptor tyrosine kinase Fer from the cadherin complex and its accumulation in the integrin complex. A peptide that mimics the first coiled-coil domain of Fer prevents Fer accumulation in the integrin complex and reverses the inhibitory effect of JMP. These findings suggest a new mechanism through which N-cadherin and β1-integrins are coordinately regulated: loss of an effector from the cytoplasmic domain of N-cadherin and gain of that effector by the β1-integrin complex.
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Ribeill, Georges. "Gestion et organisation du travail dans les compagnies de chemins de fer, des origines a 1860." Annales. Histoire, Sciences Sociales 42, no. 5 (October 1987): 999–1029. http://dx.doi.org/10.3406/ahess.1987.283434.
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L'importance de l'avènement des chemins de fer dans l'économie française est bien connue : son rôle décisif pour promouvoir ou susciter de multiples innovations depuis les questions de mobilisation financière jusqu'à celles de la politique de l'Etat en matière de service public, depuis ses effets sur les industries amont (du rail au combustible) ou les marchés aval des productions agricoles et industrielles, jusqu'à des effets structurants de géographie humaine, ont été plus ou moins fouillés. En particulier, depuis longtemps, de nombreux travaux ont été consacrés aux débats et tournants successifs de la politique publique des chemins de fer.
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Ahrén, Bo. "Regulatory peptides in the thyroid gland — a review on their localization and function." Acta Endocrinologica 124, no. 3 (March 1991): 225–32. http://dx.doi.org/10.1530/acta.0.1240225.
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Abstract. It has been demonstrated that nerve fibres storing immunoreactivity of vasoactive intestinal polypeptide, peptide histidine iso-leucine, neuropeptide Y, substance P, calcitonin gene-related peptide, galanin, and cholecystokinin exists in the thyroid, though the content of these neuropeptides is lower in the thyroid than in other organs, like in the gut. Furthermore, the parafollicular C-cells have been shown to harbour several different peptides: calcitonin, somatostatin, calcitonin gene-related peptide, gastrin-releasing peptide, katacalcin and helodermin. In addition, other regulatory peptides like atrial natriuretic hormone, growth factors, and cytokines are also produced in the thyroid. This review summarizes today's knowledge on the effects of these peptides on thyroid hormone secretion and their possible role in thyroid physiology. So far, functional studies have failed to establish any convincing effect of substance P, calcitonin gene-related peptide, galanin and cholecystokinin on basal or TSH-stimulated thyroid hormone secretion. In contrast, vasoactive intestinal peptide has convincingly been demonstrated to stimulate thyroid hormone secretion, and neuropeptide Y to potentiate the inhibitory action of noradrenaline on TSH-induced thyroid hormone secretion. This suggests that these two neuropeptides are involved in the intrathyroidal neural regulation of thyroid function. Moreover, the C-cell peptides somatostatin, calcitonin, calcitonin gene-related peptide, and katacalcin seem to be involved as inhibitors of thyroid hormone secretion, whereas both gastrin-releasing peptide and helodermin stimulate thyroid hormone secretion. Atrial natriuretic hormone and growth factors, and cytokines seem to inhibit thyroid hormone secretion. Hence, studies undertaken so far suggest a local intrathyroidal peptidergic regulatory concept, the exact role of which remains to be established.
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Casciaro, Bruno, Floriana Cappiello, Maria Rosa Loffredo, Francesca Ghirga, and Maria Luisa Mangoni. "The Potential of Frog Skin Peptides for Anti-Infective Therapies: The Case of Esculentin-1a(1-21)NH2." Current Medicinal Chemistry 27, no. 9 (March 27, 2020): 1405–19. http://dx.doi.org/10.2174/0929867326666190722095408.
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Antimicrobial Peptides (AMPs) are the key effectors of the innate immunity and represent promising molecules for the development of new antibacterial drugs. However, to achieve this goal, some problems need to be overcome: (i) the cytotoxic effects at high concentrations; (ii) the poor biostability and (iii) the difficulty in reaching the target site. Frog skin is one of the richest natural storehouses of AMPs, and over the years, many peptides have been isolated from it, characterized and classified into several families encompassing temporins, brevinins, nigrocins and esculentins. In this review, we summarized how the isolation/characterization of peptides belonging to the esculentin-1 family drove us to the design of an analogue, i.e. esculentin-1a(1-21)NH2, with a powerful antimicrobial action and immunomodulatory properties. The peptide had a wide spectrum of activity, especially against the opportunistic Gram-negative bacterium Pseudomonas aeruginosa. We described the structural features and the in vitro/in vivo biological characterization of this peptide as well as the strategies used to improve its biological properties. Among them: (i) the design of a diastereomer carrying Damino acids in order to reduce the peptide’s cytotoxicity and improve its half-life; (ii) the covalent conjugation of the peptide to gold nanoparticles or its encapsulation into poly(lactide- co-glycolide) nanoparticles; and (iii) the peptide immobilization to biomedical devices (such as silicon hydrogel contact lenses) to obtain an antibacterial surface able to reduce microbial growth and attachment. Summing up the best results obtained so far, this review traces all the steps that led these frog-skin AMPs to the direction of peptide-based drugs for clinical use.
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Zhao, Chunzhao, Omar Zayed, Zheping Yu, Wei Jiang, Peipei Zhu, Chuan-Chih Hsu, Lingrui Zhang, W. Andy Tao, Rosa Lozano-Durán, and Jian-Kang Zhu. "Leucine-rich repeat extensin proteins regulate plant salt tolerance in Arabidopsis." Proceedings of the National Academy of Sciences 115, no. 51 (December 4, 2018): 13123–28. http://dx.doi.org/10.1073/pnas.1816991115.
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The perception and relay of cell-wall signals are critical for plants to regulate growth and stress responses, but the underlying mechanisms are poorly understood. We found that the cell-wall leucine-rich repeat extensins (LRX) 3/4/5 are critical for plant salt tolerance in Arabidopsis. The LRXs physically associate with the RAPID ALKALINIZATION FACTOR (RALF) peptides RALF22/23, which in turn interact with the plasma membrane-localized receptor-like protein kinase FERONIA (FER). The lrx345 triple mutant as well as fer mutant plants display retarded growth and salt hypersensitivity, which are mimicked by overexpression of RALF22/23. Salt stress promotes S1P protease-dependent release of mature RALF22 peptides. Treatment of roots with mature RALF22/23 peptides or salt stress causes the internalization of FER. Our results suggest that the LRXs, RALFs, and FER function as a module to transduce cell-wall signals to regulate plant growth and salt stress tolerance.
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Mendez, Rufa, and Jung Kwon. "Pacific Dulse Protein: A Promising Source of Bioactive Peptides." Current Developments in Nutrition 5, Supplement_2 (June 2021): 597. http://dx.doi.org/10.1093/cdn/nzab044_028.
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Abstract Objectives Pacific dulse (Devaleraea mollis) is a protein-rich seaweed in the Pacific Northwest and increasingly being cultivated as food resource. Our previous work showed that dietary supplementation of dulse exerted beneficial metabolic effects to the high-fat fed mouse model. This study aims to evaluate the potential of the seaweed protein from dulse as a precursor for bioactive peptide (BAP) generation. Methods The potential of Pacific dulse protein as BAP precursor was assessed using in vitro and in silico approaches. Hydrolysates were prepared from the hydrated freeze-dried protein isolates which were digested using commercial proteases. These were used for the in vitro screening for antioxidant and anti-inflammatory activities as well as the inhibition of Angiotensin-converting enzyme 1 (ACE-1), Renin, and Dipeptidyl peptidase IV (DPPIV). Peptides in the hydrolysates that exhibit the highest activities were identified using de novo sequencing. Identified peptides were shortlisted based on their potential to be bioactive using Peptide Ranker and specific bioactivity scores were obtained using in silico platforms such as iDPPIV-SCM and PreAIP. To determine whether the consumption of the seaweed protein may help give rise to some bioactive peptides, annotated protein sequences of the seaweed material were obtained from UniProtKB and were subjected to in silico digestion using pepsin, chymotrypsin, and trypsin through BIOPEP. Bioactivity indices of the generated peptide fragments were recorded as predictive values. Results In silico digestion showed that dulse proteins can give rise to ACE-1, DPP-IV, and renin inhibitors, as well as antioxidant peptides. Hydrolysates exerted inhibitory effects on human ACE-1, DPPIV, and renin in vitro. ABTS radical scavenging assay and cellular antioxidant activity assay in human hepatocytes indicated the strong antioxidant potential of dulse BAP. Peptides identified through de novo sequencing had high predictive scores for DDPIV inhibition and anti-inflammatory potential. Conclusions Pacific dulse proteins is a promising precursor for the generation of BAPs that may exert beneficial health activities and support metabolic health improvement. Funding Sources Oregon State University Agricultural Research Foundation.
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Fairlie, David P., Giovanni Abbenante, and Darren R. March. "Macrocyclic Peptidomimetics Forcing Peptides into Bioactive Conformations." Current Medicinal Chemistry 2, no. 2 (August 1995): 654–86. http://dx.doi.org/10.2174/0929867302666220218001506.
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Abstract: Cyclic peptides that are potent regulators of biological processes are rapidly emerging as important mechanistic probes and drug leads. Nature clearly uses macrocycles to. constrain peptides into conformations that can selectively bind proteins or. small molecules. Therapeutic effects of such macrocycles, often containing additional conformational constraints that fine tune structure (e.g. D-amino acids, N-methyl substituents, aromatic rings, to name a few), have so far been mainly discovered by accident. However it is now becoming possible to rationally design synthetic macrocycles to selectively recognize and inhibit a specific protein. A receptor-binding struc ture is more easily adopted by macrocyclic peptidomimetics than more flexible acyclic peptides because the former have less conformational entropy. Macrocycles are often stable to hydrolysis by peptidases that degrade acyclic peptides and hydrophobic side chains can protect peptide bonds in macrocycles from hydrolysis, as well as enhance lipophilicity, cell permeability and bioavailability. Synthetic efforts to obtain bioactive conformations of short peptides have so far been substrate-based, guided by molecular modelling predictions and structure-activity data for modified amino acid sequences of substrates. However, dramatic advances in molecular biology, X-ray crystallography, NMR spectroscopy and computing are rapidly producing three dimensional structures of proteins, promising direct observation of protein-bound conformations of small molecules and receptor-based design of peptidomimetics with surface complementarity for proteins. This perspective review highlights examples of both natural and synthetic bioactive macrocyclic peptides containing constraints that fix conformation, and briefly illustrates the promise that receptor-based design holds for structural and functional mimicry of peptides by macrocycles.
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Zheng, Zihao, Aisha M. Mergaert, Irene M. Ong, Miriam A. Shelef, and Michael A. Newton. "MixTwice: large-scale hypothesis testing for peptide arrays by variance mixing." Bioinformatics 37, no. 17 (March 8, 2021): 2637–43. http://dx.doi.org/10.1093/bioinformatics/btab162.
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Abstract Summary Peptide microarrays have emerged as a powerful technology in immunoproteomics as they provide a tool to measure the abundance of different antibodies in patient serum samples. The high dimensionality and small sample size of many experiments challenge conventional statistical approaches, including those aiming to control the false discovery rate (FDR). Motivated by limitations in reproducibility and power of current methods, we advance an empirical Bayesian tool that computes local FDR statistics and local false sign rate statistics when provided with data on estimated effects and estimated standard errors from all the measured peptides. As the name suggests, the MixTwice tool involves the estimation of two mixing distributions, one on underlying effects and one on underlying variance parameters. Constrained optimization techniques provide for model fitting of mixing distributions under weak shape constraints (unimodality of the effect distribution). Numerical experiments show that MixTwice can accurately estimate generative parameters and powerfully identify non-null peptides. In a peptide array study of rheumatoid arthritis, MixTwice recovers meaningful peptide markers in one case where the signal is weak, and has strong reproducibility properties in one case where the signal is strong. Availabilityand implementation MixTwice is available as an R software package https://cran.r-project.org/web/packages/MixTwice/. Supplementary information Supplementary data are available at Bioinformatics online.
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Yang, Xiao-Yue, Di-Ying Zhong, Guo-Liang Wang, Run-Guang Zhang, and You-Lin Zhang. "Effect of Walnut Meal Peptides on Hyperlipidemia and Hepatic Lipid Metabolism in Rats Fed a High-Fat Diet." Nutrients 13, no. 5 (April 22, 2021): 1410. http://dx.doi.org/10.3390/nu13051410.
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As a natural active substance that can effectively improve blood lipid balance in the body, hypolipidemic active peptides have attracted the attention of scholars. In this study, the effect of walnut meal peptides (WMP) on lipid metabolism was investigated in rats fed a high-fat diet (HFD). The experimental results show that feeding walnut meal peptides counteracted the high-fat diet-induced increase in body, liver and epididymal fat weight, and reduce the serum concentrations of total cholesterol, triglycerides, and LDL-cholesterol and hepatic cholesterol and triglyceride content. Walnut meal peptides also resulted in increased HDL-cholesterol while reducing the atherosclerosis index (AI). Additionally, the stained pathological sections of the liver showed that the walnut meal peptides reduced hepatic steatosis and damage caused by HFD. Furthermore, walnut meal peptide supplementation was associated with normalization of elevated apolipoprotein (Apo)-B and reduced Apo-A1 induced by the high-fat diet and with favorable changes in the expression of genes related to lipid metabolism (LCAT, CYP7A1, HMGR, FAS). The results indicate that walnut meal peptides can effectively prevent the harmful effects of a high-fat diet on body weight, lipid metabolism and liver fat content in rats, and provide, and provide a reference for the further development of walnut meal functional foods.
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Moosavi, A. R. Heravi, and M. Danesh Mesgaran. "Ruminal peptide-N concentrations in Iranian Balochi lambs fed diets containing lucerne hay or silage." Proceedings of the British Society of Animal Science 2001 (2001): 145. http://dx.doi.org/10.1017/s1752756200005275.
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Peptides are intermediates in the conversion of ingested protein to ammonia in the rumen and their accumulation depends upon the nature of diet (Mesgaran & Parker, 1995). Transient accumulation of peptides occurs after feeding and then their concentrations declines. In addition, it suggests that the production of peptides in the rumen was not altered by the protein supplements when diets provided similar effective rumen degradable protein (ERDP)(Mesgaran & Moosavi, 1999). The objective of the present experiment was to investigate the effect of diets, with similar ERDP, containing lucerne hay or silage on the ruminal peptide-N concentrations.
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Vojtek, B., J. Mojzisova, L. Kulichova, P. Smrco, and M. Drazovska. "Effects of dietary nucleotides and cationic peptides on vaccination response in cats." Veterinární Medicína 66, No. 1 (January 7, 2021): 17–23. http://dx.doi.org/10.17221/35/2020-vetmed.
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Modulation of the immune system through nutrition is the aim of many studies. As the induction of a rapid onset of immunity in cats is often critical, the objective of this study was to evaluate the effects of orally administered dietary nucleotides and cationic peptides, on the vaccination response in cats. The cats were allocated to two groups: Group A (n = 8) was fed a diet with dietary nucleotides and cationic peptides for ninety-two days, and Group C (n = 8) was fed a diet without the nucleotides and cationic peptides. The cats were vaccinated against feline herpesvirus 1 (FHV-1), feline calicivirus (FCV) and feline panleukopenia virus (FPV). The proliferation activity of lymphocytes and antibody response after vaccination were evaluated using ELISA kits. Comparing the two groups, a significant increase in the proliferation activity of the lymphocytes (P < 0.01) was observed in Group A, as well as a significant increase in the antibody titres after vaccination against feline herpesvirus (P < 0.05; P < 0.001), feline calicivirus (P < 0.01; P < 0.001) and feline panleukopenia virus (P < 0.01; P < 0.001). Protective levels of the antibodies were reached significantly earlier in Group A than in Group C. In conclusion, dietary nucleotides and cationic peptides have a positive effect on the lymphocyte proliferation and antibody production after vaccination against FHV-1, FCV and FPV in cats. Therefore, we assume that they can be used as a suitable immunostimulatory substance in feline practice.
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Liang, Ningjian, Robert L. Beverly, Brian P. Scottoline, and David C. Dallas. "Peptides Derived from In Vitro and In Vivo Digestion of Human Milk Are Immunomodulatory in THP-1 Human Macrophages." Journal of Nutrition 152, no. 1 (November 9, 2021): 331–42. http://dx.doi.org/10.1093/jn/nxab350.
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ABSTRACT Background Milk proteins contain many encrypted bioactive peptides. Whether these bioactive peptides are released in the infant intestine and exert immunomodulatory activity remains unknown. Objective This study examined in vitro immunomodulatory activities of peptides from in vitro– and in vivo–digested human milk. Methods Peptides were extracted from in vitro–digested human milk and pooled intestinal samples from 8 infants fed human milk. Peptides extracted from in vitro–digested samples were fractionated. The in vitro effects of these peptides and fractions on the secretion of TNF-α and IL-8 in LPS-treated human immune THP-1 macrophages were evaluated. The significance of differences between in vitro peptide fraction treatment and control on cytokine production was analyzed by t test. LC-MS/MS–based peptidomics was conducted to identify the peptides. The peptides were screened for potential bioactivity using a sequence homology search using the Milk Bioactive Peptide Database (MBPDB). Results Six fractions of the peptide mixture extracted from the in vitro–digested human milk significantly inhibited TNF-α production by LPS-challenged THP-1 macrophages. Fractions F4, F8, F11, F14, and F17 attenuated IL-8 secretion, and F6/7 and F18 increased IL-8 secretion. Peptides extracted from the pooled in vivo intestinal samples attenuated both TNF-α and IL-8 secretion. There were 266 and 418 peptides identified in the in vitro and in vivo samples, respectively. Among the peptides, 34 and 50 in the in vitro and in vivo samples, respectively, had >80% sequence similarity to bioactive peptides in the MBPDB. Conclusions Peptides released by in vitro and in vivo infant digestion of human milk were immunomodulatory in human immune cells; fractions F4, F8, and F11 were anti-inflammatory; and F6/7 and F18 were proinflammatory. Thirteen peptides were present in all fractions with anti-inflammatory activity, and 38 peptides were present in all fractions with proinflammatory activity. These peptides potentially contributed to the observed immunomodulatory activity of the peptide mixtures.
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Moosavi, A. R. Heravi, and M. Danesh Mesgaran. "Ruminal peptide and soluble protein N concentrations in Iranian Baloochi lambs fed diets containing lucerne hay or silage." Proceedings of the British Society of Animal Science 2002 (2002): 146. http://dx.doi.org/10.1017/s1752756200008024.
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It is generally agreed that peptides accumulate in the rumen fluid after feeding. It has been also suggested that the production of peptides in the rumen was not altered by the protein supplements when diets provided similar effective rumen degradable protein (Mesgaran & Moosavi, 1999). The objective of the present experiment was to investigate the effect of diets containing lucerne hay or silage treated by urea and formaldehyde on the ruminal peptide and soluble protein N concentrations in Iranian Baloochi lambs.
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Kellner, Michael, Ines Diehl, Kristina Knaudt, Cornelius Schüle, Holger Jahn, and Klaus Wiedemann. "C-type natriuretic peptide exerts stimulatory effects on the corticotropin-releasing hormone-induced secretion of hormones in normal man." European Journal of Endocrinology 136, no. 4 (April 1997): 388–93. http://dx.doi.org/10.1530/eje.0.1360388.
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Abstract C-type natriuretic peptide and atrial natriuretic peptide have been reported to bind to distinct receptors and to exert opposing effects on different systems. Although it is known that atrial natriuretic peptide inhibits the corticotropin-releasing hormone-stimulated hormone release in man, the corresponding action of C-type natriuretic peptide has so far not been characterized. We investigated the effects of 30-min infusions of 150 and 300 μg C-type natriuretic peptide on adrenocorticotropin, cortisol, and prolactin release stimulated by 100 μg corticotropin-releasing hormone and on cardiovascular parameters in 8 healthy male volunteers. Compared with placebo, 300 μg C-type natriuretic peptide significantly (P<0·05) enhanced the stimulation of cortisol (area under curve (arbitrary units): 520 ± 35 vs 651 ± 55) and prolactin (area under curve: 29 ± 3 vs 37 ± 5). Adrenocorticotropin levels were increased, but the differences did not reach statistical significance (maximum increment: 27±4 vs 36± 2 pg/ml). C-type natriuretic peptide at a dose of 150 μg had no clear effect on these hormones and C-type natriuretic peptide also produced no cardiovascular or subjective effects. Our data suggest stimulatory effects of C-type natriuretic peptide on corticotropinreleasing hormone-induced hormone release and offer further evidence for a complex role of different natriuretic peptides in endocrine regulation. European Journal of Endocrinology 136 388–393
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Wallace, R. J., C. J. Newbold, and N. McKain. "Influence of ionophores and energy inhibitors on peptide metabolism by rumen bacteria." Journal of Agricultural Science 115, no. 2 (October 1990): 285–90. http://dx.doi.org/10.1017/s0021859600075250.
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SUMMARYIonophores and inhibitors of bacterial energy metabolism were added to mixed rumen bacteria prepared from sheep receiving grass hay plus concentrate diets, and their influence on the rate of metabolism of alanine (Ala) peptides was determined. Dicyclohexylcarbodiimide (DCCD) had no influence on the rate of breakdown of Ala2, Ala3, Ala4or Ala5, indicating that the metabolism of these peptides did not require ATP. The protonophores tetrachlorosalicylanilide (TCS) and carbonyl cyanidem-chlorophenyl-hydrazone (CCCP) inhibited peptide breakdown to a minor extent (< 15%), whereas the ionophores monensin and tetronasin had greater, but still small (12–31%), inhibitory effects. Toluene stimulated peptide breakdown, consistent with a permeability barrier having been removed. Thus, at least some peptide metabolism depends on transport into bacteria; transport appears not to be ATP-linked, and may well be coupled to the uptake of mineral cations rather than protons. Rumen fluid from sheep receiving a similar diet with added monensin (33 mg/kg) or tetronasin (10 mg/kg) hydrolysed Ala3and Ala4at rates that did not differ significantly from controls. Nevertheless, the peak concentration of free peptides in rumen fluid after feeding was more than doubled in ionophore-fed sheep, and peptides persisted for longer than in control animals.
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Liu, Chen, Lianping Shen, Yu Xiao, David Vyshedsky, Chao Peng, Xiang Sun, Zhiwen Liu, et al. "Pollen PCP-B peptides unlock a stigma peptide–receptor kinase gating mechanism for pollination." Science 372, no. 6538 (April 8, 2021): 171–75. http://dx.doi.org/10.1126/science.abc6107.
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Sexual reproduction in angiosperms relies on precise communications between the pollen and pistil. The molecular mechanisms underlying these communications remain elusive. We established that in Arabidopsis, a stigmatic gatekeeper, the ANJEA–FERONIA (ANJ–FER) receptor kinase complex, perceives the RAPID ALKALINIZATION FACTOR peptides RALF23 and RALF33 to induce reactive oxygen species (ROS) production in the stigma papillae, whereas pollination reduces stigmatic ROS, allowing pollen hydration. Upon pollination, the POLLEN COAT PROTEIN B-class peptides (PCP-Bs) compete with RALF23/33 for binding to the ANJ–FER complex, leading to a decline of stigmatic ROS that facilitates pollen hydration. Our results elucidate a molecular gating mechanism in which distinct peptide classes from pollen compete with stigma peptides for interaction with a stigmatic receptor kinase complex, allowing the pollen to hydrate and germinate.
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Danesh Mesgaran, M., and A. R. H. Moosavi. "Effects of diets formulated to contain similar amounts of ERDP with different protein sources on ruminal peptide-N concentrations in Iranian Baloochi lambs." Proceedings of the British Society of Animal Science 1999 (1999): 110. http://dx.doi.org/10.1017/s1752756200002659.
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Peptides are intermediates in the conversion of ingested protein to ammonia in the rumen and their accumulation depends upon the nature of dietary protein (Mesgaran & Parker, 1995). In addition, It has been demonstrated that the hydrolysis rate of peptides was influenced by peptide structure and that proline containing peptides were hydrolysed more slowly by rumen fluid (Mesgaran & Parker, 1996). The objective of the present experiment was to investigate the effect of altering the sources of protein, in diets with similar effective rumen degradable protein (ERDP), on the ruminal peptide-N concentrations.Four Iranian Baloochi lambs weighing 33±1.3 Kg, each with a permanent rumen fistula, were fed twice daily with diets differing in protein sources in a 42 latin square design. The diets consisted of a basal diet of chopped lucerne, barely and sugar beet pulp (190, 230 and 170 g DM d–1, respectively) which was supplemented with lucerne (L), cottonseed meal (C), soybean meal (S) or molasses+urea (M+U) (210, 118, 84 and 80+9 g DM d–1, respectively).
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Merger, Michèle. "Les chemins de fer italiens : leur construction et leurs effets amont (1860-1915)." Histoire, économie et société 11, no. 1 (1992): 109–29. http://dx.doi.org/10.3406/hes.1992.1626.
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Le Bollan, Christophe. "L’arrivée du chemin de fer à Brest ou les effets d’une logique stratégique." Revue d’histoire des chemins de fer, no. 38 (May 31, 2008): 72–86. http://dx.doi.org/10.4000/rhcf.420.
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Lebenthal, Emanuel. "Gastrointestinal Maturation and Motility Patterns as Indicators for Feeding the Premature Infant." Pediatrics 95, no. 2 (February 1, 1995): 209. http://dx.doi.org/10.1542/peds.95.2.209.
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The Koenig et al study1 showed different effects of two-thirds concentration feeding compared with one-third concentration in relation to shorter mean time of onset and longer duration of fed response. The different motility response can be related to availability of regulatory mechanisms. Similar studies of individual food component,26 eg, glucose, triglyceride, and casein hydrolysate, disrupted fasting activity but had differing effects on the duration of fed activity and the increase of contractile activity. Glucose followed by peptides then lipids caused the greatest increase in contraction and duration of fed activity.26 It is assumed that each group of nutrients induces the secretion of different peptide hormones that may be responsible for the fed pattern of motility. It is suggested that the feeding releases gastrin and cholecystokinin27 that in return change the pattern of motility activity to the fed pattern. When a protein feeding was given intraduodenally both cholecystokinin and pancreatic polypeptide were released in large quantities and the intestinal motility changed to fed pattern.27 Peptide YY is also released in large quantities after both a large protein and fatty meal.28 The main question that the Koenig et al study1 raises is how the concentration, volume, and presence of the feed in the stomach or duodenum affect the release of regulatory gut peptides and gastrointestinal hormones. In addition it is important to know how the ontogeny of gut hormones and regulatory peptide can be manipulated by changing the mode, content, concentration, and volume of feeding. Available fat, carbohydrate, and protein in the premature diet might be important in modifying the developmental pattern of intestinal and pancreatic enzymes as well as affecting gastric emptying.
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Yamada, Chihiro. "Involvement of Ghrelin Dynamics in Stress-Induced Eating Disorder: Effects of Sex and Aging." International Journal of Molecular Sciences 22, no. 21 (October 28, 2021): 11695. http://dx.doi.org/10.3390/ijms222111695.
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Stress, a factor that affects appetite in our daily lives, enhances or suppresses appetite and changes palatability. However, so far, the mechanisms underlying the link between stress and eating have not been fully elucidated. Among the peripherally produced appetite-related peptides, ghrelin is the only orexigenic peptide, and abnormalities in the dynamics and reactivity of this peptide are involved in appetite abnormalities in various diseases and psychological states. This review presents an overview of the research results of studies evaluating the effects of various stresses on appetite. The first half of this review describes the relationship between appetite and stress, and the second half describes the relationship between the appetite-promoting peptide ghrelin and stress. The effects of sex differences and aging under stress on appetite are also described.
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Bouzid, Rachid, Monique T. A. de Beijer, Robbie J. Luijten, Karel Bezstarosti, Amy L. Kessler, Marco J. Bruno, Maikel P. Peppelenbosch, Jeroen A. A. Demmers, and Sonja I. Buschow. "Empirical Evaluation of the Use of Computational HLA Binding as an Early Filter to the Mass Spectrometry-Based Epitope Discovery Workflow." Cancers 13, no. 10 (May 12, 2021): 2307. http://dx.doi.org/10.3390/cancers13102307.
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Immunopeptidomics is used to identify novel epitopes for (therapeutic) vaccination strategies in cancer and infectious disease. Various false discovery rates (FDRs) are applied in the field when converting liquid chromatography-tandem mass spectrometry (LC-MS/MS) spectra to peptides. Subsequently, large efforts have recently been made to rescue peptides of lower confidence. However, it remains unclear what the overall relation is between the FDR threshold and the percentage of obtained HLA-binders. We here directly evaluated the effect of varying FDR thresholds on the resulting immunopeptidomes of HLA-eluates from human cancer cell lines and primary hepatocyte isolates using HLA-binding algorithms. Additional peptides obtained using less stringent FDR-thresholds, although generally derived from poorer spectra, still contained a high amount of HLA-binders and confirmed recently developed tools that tap into this pool of otherwise ignored peptides. Most of these peptides were identified with improved confidence when cell input was increased, supporting the validity and potential of these identifications. Altogether, our data suggest that increasing the FDR threshold for peptide identification in conjunction with data filtering by HLA-binding prediction, is a valid and highly potent method to more efficient exhaustion of immunopeptidome datasets for epitope discovery and reveals the extent of peptides to be rescued by recently developed algorithms.
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Abdelhedi, Ola, Hana Khemakhem, Rim Nasri, Mourad Jridi, Leticia Mora, Ikram Ben Amor, Kamel Jamoussi, Fidel Toldrá, Jalel Gargouri, and Moncef Nasri. "Assessment of Cholesterol, Glycemia Control and Short- and Long-Term Antihypertensive Effects of Smooth Hound Viscera Peptides in High-Salt and Fructose Diet-Fed Wistar Rats." Marine Drugs 17, no. 4 (March 27, 2019): 194. http://dx.doi.org/10.3390/md17040194.
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In this study, the antihypertensive activity of Purafect®-smooth hound viscera protein hydrolysate (VPH) and its peptide fraction with molecular weight (MW) below 1 kDa (VPH-I) was investigated. In addition, the lipase inhibitory activity, as well the anticoagulant potential, in vitro, were assessed. The antihypertensive effects of VPH and VPH-I were studied during 24 h (short-term effect) and 30 days (long-term effect) using high-salt (18% NaCl) and -fructose (10%) diet (HSFD)-induced hypertension. Data showed that, 4 h post-administration of VPH and VPH-I (200 mg/kg BW), the systolic blood pressure of rats was reduced by about 6 and 9 mmHg, respectively. These effects were similar to that obtained with Captopril (~9 mmHg at t = 4 h). On the other hand, exposing the rats to daily to HSFD, coupled to the administration of viscera peptides, was found to attenuate hypertension. In addition, the proteins’ treatments were able to correct lipid and glycemic disorders, by reducing the total cholesterol and triglyceride contents and resorting to the plasma glucose level, compared to the HSFD group. Overall, the present findings demonstrated the preventive effect of VPH-peptides from hypertension complications, as a result of their biological properties.
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Pantako, Odile T., Lise Lemieux, and Jean Amiot. "The effects of α-lactabumin and whey protein concentrate on dry matter recovery, TCA soluble protein levels, and peptide distribution in the rat gastrointestinal tract." Canadian Journal of Physiology and Pharmacology 79, no. 4 (April 1, 2001): 320–28. http://dx.doi.org/10.1139/y00-126.
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The effects of two dietary proteins on dry matter recovery, trichloroacetic acid (TCA) soluble protein concentration, and peptide distribution in gastrointestinal contents were investigated in rats trained to consume, in a single 2-hour daily meal, diets containing α-lactalbumin (α-LA) or whey protein concentrate (WPC) for two weeks. Compared with the WPC diet, the α-LA diet emptied faster from the stomach. Dry matter recovery was higher in the stomach contents of rats fed the WPC diet than in those given the α-LA diet, but dry matter content in the small intestine was comparable. TCA soluble protein levels in the stomach and the small intestinal contents were also significantly (P < 0.001) higher in rats fed the WPC diet. The concentration of peptides having molecular weights (MW) ranging from 12 50030 000 daltons (Da) was higher in the stomach contents of rats fed the WPC diet. Conversely, the level of peptides ranging from 500012 500 Da was higher in the stomach contents of rats fed the α-LA diet. For both diets, the small intestinal contents were characterized by high levels of amino acids and small peptides. These results suggest that the hydrolysis and absorption of α-LA is faster than that of WPC.Key words: In vivo protein digestion, peptides absorption, whey protein concentrate, α-lactalbumin, stomach emptying.
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Santos, André L. S., Filipe P. Matteoli, Leandro S. Sangenito, Marta H. Branquinha, Bruno A. Cotrim, and Gabriel O. Resende. "Asymmetric peptidomimetics containing L-tartaric acid core inhibit the aspartyl peptidase activity and growth of Leishmania amazonensis promastigotes." Acta Parasitologica 63, no. 1 (March 26, 2018): 114–24. http://dx.doi.org/10.1515/ap-2018-0013.
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AbstractAspartyl-type peptidases are promising chemotherapeutic targets in protozoan parasites. In the present work, we identified an aspartyl peptidase activity from the soluble extract ofLeishmania amazonensispromastigotes, which cleaved the fluorogenic peptide 7-methoxycoumarin-4-acetyl-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys(DNP)-D-Arg-amide (cathepsin D substrate) under acidic pH conditions at 37°C, showing aKMof 0.58 μM andVmaxof 129.87 fluorescence arbitrary units/s mg protein. The leishmanial aspartyl peptidase activity was blocked by pepstatin A (IC50= 6.8 μM) and diazo-acetyl-norleucinemetilester (IC50= 10.2 μM), two classical aspartyl peptidase inhibitors. Subsequently, the effects of 6 asymmetric peptidomimetics, containingL-tartaric acid core, were tested on both aspartyl peptidase and growth ofL.amazonensispromastigotes. The peptidomimetics named 88, 154 and 158 promoted a reduction of 50% on the leishmanial aspartyl peptidase activity at concentrations ranging from 40 to 85 μM, whereas the peptidomimetic 157 was by far the most effective, presenting IC50of 0.04 μM. Furthermore, the peptidomimetics 157 and 154 reduced the parasite proliferation in a dose-dependent manner, displaying IC50values of 33.7 and 44.5 μM, respectively. Collectively, the peptidomimetic 157 was the most efficient compound able to arrest both aspartyl peptidase activity and leishmanial proliferation, which raises excellent perspectives regarding its use against this human pathogenic protozoan.
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Pasco, Sylvie, Laurent Ramont, François-Xavier Maquart, and Jean-Claude Monboisse. "Effets biologiques de peptides des collagènes I et IV." Journal de la Société de Biologie 197, no. 1 (2003): 31–39. http://dx.doi.org/10.1051/jbio/2003197010031.
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Martin, Christine M. A., Vadivel Parthsarathy, Varun Pathak, Victor A. Gault, Peter R. Flatt, and Nigel Irwin. "Characterisation of the biological activity of xenin-25 degradation fragment peptides." Journal of Endocrinology 221, no. 2 (February 11, 2014): 193–200. http://dx.doi.org/10.1530/joe-13-0617.
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Xenin-25, a peptide co-secreted with the incretin hormone glucose-dependent insulinotropic polypeptide (GIP), possesses promising therapeutic actions for obesity-diabetes. However, native xenin-25 is rapidly degraded by serum enzymes to yield the truncated metabolites: xenin 9–25, xenin 11–25, xenin 14–25 and xenin 18–25. This study has examined the biological activities of these fragment peptides. In vitro studies using BRIN-BD11 cells demonstrated that native xenin-25 and xenin 18–25 possessed significant (P<0.05 to P<0.001) insulin-releasing actions at 5.6 and 16.7 mM glucose, respectively, but not at 1.1 mM glucose. In addition, xenin 18–25 significantly (P<0.05) potentiated the insulin-releasing action of the stable GIP mimetic (d-Ala2)GIP. In contrast, xenin 9–25, xenin 11–25 and xenin 14–25 displayed neither insulinotropic nor GIP-potentiating actions. Moreover, xenin 9–25, xenin 11–25 and xenin 14–25 significantly (P<0.05 to P<0.001) inhibited xenin-25 (10−6 M)-induced insulin release in vitro. I.p. administration of xenin-based peptides in combination with glucose to high fat-fed mice did not significantly affect the glycaemic excursion or glucose-induced insulin release compared with controls. However, when combined with (d-Ala2)GIP, all xenin peptides significantly (P<0.01 to P<0.001) reduced the overall glycaemic excursion, albeit to a similar extent as (d-Ala2)GIP alone. Xenin-25 and xenin 18–25 also imparted a potential synergistic effect on (d-Ala2)GIP-induced insulin release in high fat-fed mice. All xenin-based peptides lacked significant satiety effects in normal mice. These data demonstrate that the C-terminally derived fragment peptide of xenin-25, xenin 18–25, exhibits significant biological actions that could have therapeutic utility for obesity-diabetes.
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Wei, Xiaoyuan, Tsungcheng Tsai, Joshua Knapp, Kristopher Bottoms, Feilong Deng, Robert Story, Charles Maxwell, and Jiangchao Zhao. "ZnO Modulates Swine Gut Microbiota and Improves Growth Performance of Nursery Pigs When Combined with Peptide Cocktail." Microorganisms 8, no. 2 (January 21, 2020): 146. http://dx.doi.org/10.3390/microorganisms8020146.
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Zinc has been very efficacious in reducing post-weaning diarrhea, whereas animal-derived peptides are suggested to improve the growth performance of weaned piglets. However, the combined effect of zinc and peptides on swine production and swine gut microbiota is still largely unknown. In this study, we followed 288 nursery pigs from the age of d30 to d60 to evaluate the growth performance and gut microbiota of weanling pigs subjected to different levels of a fish-porcine-microbial peptide cocktail (0.05%, 0.25%, and 0.5%) with or without the pharmaceutical level of zinc oxide (ZnO) (2500 ppm) supplementation in a nutrient-deficient diet. Rectal swab samples were collected from pigs with body weight (BW) approach average at each pen on d30, d42, and d60 to determine gut microbiota. Average daily gain (ADG) and BW in piglets fed high zinc (HZ) increased with increasing levels of peptide. The microbiota of the HZ group also diverged from those of the standard zinc (SZ) group from d30 to d60. Adding peptide did not alter community structure regardless of zinc supplementation. Collectively, these findings demonstrated that the pharmaceutical level of zinc as ZnO conditioned the gut community to the point where peptide could effectively restore growth performance in nursery pigs fed nutrient-deficient diets.
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Yang, Wenzhu, YiZhao Shen, Ranithri Abeynayakea, Tao Ran, and Lingyun Chen. "PSIX-12 Screening of peptides for their impact of protease, protease dose and peptide dose on in vitro rumen dry matter digestibility." Journal of Animal Science 97, Supplement_3 (December 2019): 398–99. http://dx.doi.org/10.1093/jas/skz258.794.
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Abstract The objective of this study was to screening peptides for the effects on in vitro rumen dry matter (DM) digestibility (DMD) of feeds in batch culture. Three brewers spent grain (BSG) samples from different batches were obtained from a local brewery. Peptides were developed with BSG protein varying protease (alcalase, everlase, flavourzyme) and protease dosages (protease:BSG protein; 1:100, 5:100, 10:100, 15:100) under optimum pH and temperature conditions. In total, 36 peptides were produced and screened. A series of batch cultures were conducted and substrates were barley silage and barley grain. The experiment was a complete randomized design with a factorial arrangement; 3 proteases × 4 protease doses + 4 doses of each peptide (0, 0.5, 1.0, 1.5% of substrate DM) with 3 replications of each treatment combination. Rumen inoculum was from three rumen fistulated beef heifers fed a diet consisting of 10% silage and 90% concentrate (DM basis). The incubation was conducted at 39°C for 24 h. Interactions among protease, protease dose and peptide dose were not significant. For barley grain, DMD differed (P < 0.01) among proteases (85.2, 72.3, 65.2%, respectively, for alcalase, flavourzise, everlase). Increasing peptide doses from 0, 0.5, 1.0 to 1.5% linearly (P < 0.01) decreased the DMD from 88 to 78% (alcalase), 69 to 59% (everlase) and 78 to 67% (flavourzyme); whereas protease dose did not affect the DMD. With barley silage, the DMD was higher (P < 0.05) with flavourzyme (65.3%) than alcalase (59.2%) or everlase (61.2%); in contrast, the DMD was affected neither by protease dose nor by the peptide dose, except that increasing supplementation of peptide derived from everlase linearly (P < 0.05) decreased the DMD (65.1 to 58.9%). These results indicated that the peptides derived from BSG decreased in vitro rumen feed digestibility, which varied with proteases, peptide dose or feeds.
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Lu, Hongyan, Li Fang, Xiyan Wang, Dan Wu, Chunlei Liu, Xiaoting Liu, Ji Wang, Yawen Gao, and Weihong Min. "Structure-Activity Relationship of Pine Nut-Derived Peptides and Their Protective Effect on Nerve-Cell Mitochondria." Foods 11, no. 10 (May 15, 2022): 1428. http://dx.doi.org/10.3390/foods11101428.
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This study aimed to investigate the structure-activity relationship of the pine nut antioxidant peptide WYPGK and its derivative peptides, and to evaluate the protective effect of the latter on oxidative damage to mitochondrial structure and function in PC12 cells. Molecular docking revealed the derivative peptides WYFGK and WYSGK to have higher affinity to the active region of sirtuin 3 (SIRT3) (−6.08 kcal/mol and −5.87 kcal/mol, respectively), hence indicating that they are promising SIRT3 inducers and antioxidant factors. The derivative peptide WYSGK presented the highest ORAC value (5457.70 µmol TE/g), ABTS scavenging activity (70.05%), and Fe2+-chelating activity (81.70%), followed by WYPGK and WYFGK. Circular dichroism and nuclear magnetic resonance data suggested that the presence of 3-Ser in WYSGK increased its β-sheet content, and that the active hydrogen atoms produced chemical shifts. In H2O2-induced PC12 cells, WYSGK substantially reduced ROS and MDA levels, and increased ATP levels. Transmission electron microscopy and Seahorse Analyze assay proved the peptide WYSGK to significantly alleviate mitochondrial damage and respiratory dysfunction (p < 0.05), thereby implying that a study of structure-activity relationships of the peptides can possibly be an effective approach for the development of functional factors.
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Reid, Scott W., Steve McAdam, Kathrine J. Smith, Paul Klenerman, Chris A. O'Callaghan, Karl Harlos, Bent K. Jakobsen, et al. "Antagonist HIV-1 Gag Peptides Induce Structural Changes in HLA B8." Journal of Experimental Medicine 184, no. 6 (December 1, 1996): 2279–86. http://dx.doi.org/10.1084/jem.184.6.2279.
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In the cellular immune response, recognition by CTL-TCRs of viral antigens presented as peptides by HLA class I molecules, triggers destruction of the virally infected cell (Townsend, A.R.M., J. Rothbard, F.M. Gotch, G. Bahadur, D. Wraith, and A.J. McMichael. 1986. Cell. 44:959–968). Altered peptide ligands (APLs) which antagonise CTL recognition of infected cells have been reported (Jameson, S.C., F.R. Carbone, and M.J. Bevan. 1993. J. Exp. Med. 177:1541–1550). In one example, lysis of antigen presenting cells by CTLs in response to recognition of an HLA B8–restricted HIV-1 P17 (aa 24–31) epitope can be inhibited by naturally occurring variants of this peptide, which act as TCR antagonists (Klenerman, P., S. Rowland Jones, S. McAdam, J. Edwards, S. Daenke, D. Lalloo, B. Koppe, W. Rosenberg, D. Boyd, A. Edwards, P. Giangrande, R.E. Phillips, and A. McMichael. 1994. Nature (Lond.). 369:403– 407). We have characterised two CTL clones and a CTL line whose interactions with these variants of P17 (aa 24–31) exhibit a variety of responses. We have examined the high resolution crystal structures of four of these APLs in complex with HLA B8 to determine alterations in the shape, chemistry, and local flexibility of the TCR binding surface. The variant peptides cause changes in the recognition surface by three mechanisms: changes contributed directly by the peptide, effects transmitted to the exposed peptide surface, and induced effects on the exposed framework of the peptide binding groove. While the first two mechanisms frequently lead to antagonism, the third has more profound effects on TCR recognition.
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Zabielski, Romuald, Claude Dardillat, Isabelle Le Huërou-Luron, Christine Bernard, Jean Alain Chayvialle, and Paul Guilloteau. "Periodic fluctuations of gut regulatory peptides in phase with the duodenal migrating myoelectric complex in preruminant calves: effect of different sources of dietary protein." British Journal of Nutrition 79, no. 3 (March 1998): 287–96. http://dx.doi.org/10.1079/bjn19980046.
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Four preruminant calves with implanted electrodes in the duodenum and a catheter in the external jugular vein were used for investigation of plasma gut regulatory peptide profiles during different phases of migrating myoelectric complex (MMC) in the small intestine. The effects of different dietary proteins on the rhythmic activity of gut peptides and gastrointestinal motility were compared. In particular, the effects of skimmed-milk protein (retaining physiological patterns of abomasal clotting, and abomaso-intestinal digesta flow)v.fish protein (devoid of clotting activity and modifying the digesta flow) were studied. In calves fed on the milk diet, plasma concentrations of pancreatic polypeptide, motilin, secretin, cholecystokinin (CCK) and somatostatin, but not vasoactive intestinal polypeptide or gastrin, fluctuated in phase with the duodenal MMC in the preprandial period. Feeding transiently affected the intestinal MMC and abolished the peptide fluctuations in a specimen-specific manner. In contrast, calves fed on the fish-protein diet showed more profound changes in intestinal MMC. In these animals the MMC-related fluctuations were significant only for plasma CCK. In conclusion, the source of dietary protein has an impact on the physiological endocrine function of the small intestine. Observed fluctuations of plasma gut regulatory peptides seem to be secondary to duodenal motility cycles.
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Shi, Wanxia, Pengchen He, Xian-Chun Zeng, Weiwei Wu, and Xiaoming Chen. "Inhibitory Effect of an Acidic Peptide on the Activity of an Antimicrobial Peptide from the Scorpion Mesobuthus martensii Karsch." Molecules 23, no. 12 (December 14, 2018): 3314. http://dx.doi.org/10.3390/molecules23123314.
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Highly acidic peptides with no disulfide bridges are widely present in the scorpion venoms; however, none of them has been functionally characterized so far. Here, we cloned the full-length cDNA of a short-chain highly acidic peptide (referred to as HAP-1) from a cDNA library made from the venom glands of the Chinese scorpion Mesobuthus martensii Karsch. HAP-1 contains 19 amino acid residues with a predicted IP value of 4.25. Acidic amino residues account for 33.3% of the total residues in the molecule of HAP-1. HAP-1 shows 76–98% identities to some scorpion venom peptides that have not yet been functionally characterized. Secondary structure prediction showed that HAP-1 contains a beta-sheet region (residues 9–17), and two coiled coil regions (residues 1–8 and 18–19) located at the N-terminal and C-terminal regions of the peptide, respectively. Antimicrobial assay showed that HAP-1 does not have any effect on the growth of the bacterium Staphylococcus aureus AB94004. However, it potently inhibits the antimicrobial activity of a 13-mer peptide from M. martensii Karsch against Staphylococcus aureus AB94004. This finding is the first characterization of the function of such highly acidic peptides from scorpions.
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Gil-Lozano, Manuel, Diego Pérez-Tilve, Mayte Alvarez-Crespo, Aurelio Martís, Ana M. Fernandez, Pablo A. F. Catalina, Lucas C. Gonzalez-Matias, and Federico Mallo. "GLP-1(7-36)-amide and Exendin-4 Stimulate the HPA Axis in Rodents and Humans." Endocrinology 151, no. 6 (April 2, 2010): 2629–40. http://dx.doi.org/10.1210/en.2009-0915.
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Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic peptide expressed in the gut and brain, which is secreted in response to food intake. The levels of GLP-1 within the brain have been related to the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and hence, this peptide might mediate some responses to stress. Nevertheless, there is little information regarding the effects of circulating GLP-1 on the neuroendocrine control of HPA activity. Here, we have studied the response of corticoadrenal steroids to the peripheral administration of GLP-1 (7-36)-amide and related peptides [exendin (Ex)-3, Ex-4, and Ex-4(3-39)] in rats, mice, and humans. GLP-1 increases circulating corticosterone levels in a time-dependent manner, both in conscious and anaesthetized rats, and it has also increased aldosterone levels. Moreover, GLP-1 augmented cortisol levels in healthy subjects and diabetes mellitus (DM)-1 patients. The effects of GLP-1/Ex-4 on the HPA axis are very consistent after distinct means of administration (intracerebroventricular, iv, and ip), irrespective of the metabolic state of the animals (fasting or fed ad libitum), and they were reproduced by different peptides in this family, independent of glycaemic changes and their insulinotropic properties. Indeed, these effects were also observed in diabetic subjects (DM-1 patients) and in the DM-1 streptozotocin-rat or DM-2 muscle IGF-I receptor-lysine-arginine transgenic mouse animal models. The mechanisms whereby circulating GLP-1 activates the HPA axis remain to be elucidated, although an increase in ACTH after Ex-4 and GLP-1 administration implicates the central nervous system or a direct effect on the pituitary. Together, these findings suggest that GLP-1 may play an important role in regulating the HPA axis.
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Lupi, Laura, Brenda Bracco, Paola Sassi, Silvia Corezzi, Assunta Morresi, Daniele Fioretto, Lucia Comez, and Marco Paolantoni. "Hydration Dynamics of Model Peptides with Different Hydrophobic Character." Life 12, no. 4 (April 12, 2022): 572. http://dx.doi.org/10.3390/life12040572.
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The multi-scale dynamics of aqueous solutions of the hydrophilic peptide N-acetyl-glycine-methylamide (NAGMA) have been investigated through extended frequency-range depolarized light scattering (EDLS), which enables the broad-band detection of collective polarizability anisotropy fluctuations. The results have been compared to those obtained for N-acetyl-leucinemethylamide (NALMA), an amphiphilic peptide which shares with NAGMA the same polar backbone, but also contains an apolar group. Our study indicates that the two model peptides induce similar effects on the fast translational dynamics of surrounding water. Both systems slow down the mobility of solvating water molecules by a factor 6–8, with respect to the bulk. Moreover, the two peptides cause a comparable far-reaching spatial perturbation extending to more than two hydration layers in diluted conditions. The observed concentration dependence of the hydration number is explained considering the random superposition of different hydration shells, while no indication of solute aggregation phenomena has been found. The results indicate that the effect on the dynamics of water solvating the amphiphilic peptide is dominated by the hydrophilic backbone. The minor impact of the hydrophobic moiety on hydration features is consistent with structural findings derived by Fourier transform infrared (FTIR) measurements, performed in attenuated total reflectance (ATR) configuration. Additionally, we give evidence that, for both systems, the relaxation mode in the GHz frequency range probed by EDLS is related to solute rotational dynamics. The rotation of NALMA occurs at higher timescales, with respect to the rotation of NAGMA; both processes are significantly slower than the structural dynamics of hydration water, suggesting that solute and solvent motions are uncoupled. Finally, our results do not indicate the presence of super-slow water (relaxation times in the order of tens of picoseconds) around the peptides investigated.
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Finn, Patricia D., David Rodriguez, Jill Kohler, Zhengfeng Jiang, Sindy Wan, Erick Blanco, Andrew J. King, et al. "Intestinal TGR5 agonism improves hepatic steatosis and insulin sensitivity in Western diet-fed mice." American Journal of Physiology-Gastrointestinal and Liver Physiology 316, no. 3 (March 1, 2019): G412—G424. http://dx.doi.org/10.1152/ajpgi.00300.2018.
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Takeda G protein-coupled receptor 5 (TGR5) agonists induce systemic release of glucagon-like peptides (GLPs) from intestinal L cells, a potentially therapeutic action against metabolic diseases such as nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), and Type 2 diabetes. Historically, TGR5 agonist use has been hindered by side effects, including inhibition of gallbladder emptying. Here, we characterize RDX8940, a novel, orally administered TGR5 agonist designed to have minimal systemic effects and investigate its activity in mice fed a Western diet, a model of NAFLD and mild insulin resistance. Agonist activity, binding selectivity, toxicity, solubility, and permeability of RDX8940 were characterized in standard in vitro models. RDX8940 pharmacokinetics and effects on GLP secretion, insulin sensitivity, and liver steatosis were assessed in C57BL/6 mice fed normal or Western diet chow and given single or repeated doses of RDX8940 or vehicle, with or without dipeptidyl peptidase-4 (DPP4) inhibitors. Gallbladder effects were assessed in CD-1 mice fed normal chow and given RDX8940 or a systemic TGR5 agonist or vehicle. Our results showed that RDX8940 is minimally systemic, potent, and selective, and induces incretin (GLP-1, GLP-2, and peptide YY) secretion. RDX8940-induced increases in plasma active GLP-1 (aGLP-1) levels were enhanced by repeated dosing and by coadministration of DPP4 inhibitors. RDX8940 increased hepatic exposure to aGLP-1 without requiring coadministration of a DPP4 inhibitor. In mice fed a Western diet, RDX8940 improved liver steatosis and insulin sensitivity. Unlike systemic TGR5 agonists, RDX8940 did not inhibit gallbladder emptying. These results indicate that RDX8940 may have therapeutic potential in patients with NAFLD/NASH. NEW & NOTEWORTHY Takeda G protein-coupled receptor 5 (TGR5) agonists have potential as a treatment for nonalcoholic steatohepatitis and nonalcoholic fatty liver disease (NAFLD) but have until now been associated with undesirable side effects associated with systemic TGR5 agonism, including blockade of gallbladder emptying. We demonstrate that RDX8940, a potent, selective, minimally systemic oral TGR5 agonist, improves liver steatosis and insulin sensitivity in a mouse model of NAFLD and does not inhibit gallbladder emptying in mice.
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Kogut, Michael H., Kenneth J. Genovese, Haiqi He, Christina L. Swaggerty, and Yiwei Jiang. "Modulation of Chicken Intestinal Immune Gene Expression by Small Cationic Peptides as Feed Additives during the First Week Posthatch." Clinical and Vaccine Immunology 20, no. 9 (July 17, 2013): 1440–48. http://dx.doi.org/10.1128/cvi.00322-13.
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ABSTRACTWe have been investigating modulation strategies tailored around the selective stimulation of the host's immune system as an alternative to direct targeting of microbial pathogens by antibiotics. One such approach is the use of a group of small cationic peptides (BT) produced by a Gram-positive soil bacterium,Brevibacillus texasporus. These peptides have immune modulatory properties that enhance both leukocyte functional efficiency and leukocyte proinflammatory cytokine and chemokine mRNA transcription activitiesin vitro. In addition, when provided as a feed additive for just 4 days posthatch, BT peptides significantly induce a concentration-dependent protection against cecal and extraintestinal colonization bySalmonella entericaserovar Enteritidis. In the present studies, we assessed the effects of feeding BT peptides on transcriptional changes on proinflammatory cytokines, inflammatory chemokines, and Toll-like receptors (TLR) in the ceca of broiler chickens with and withoutS. Enteritidis infection. After feeding a BT peptide-supplemented diet for the first 4 days posthatch, chickens were then challenged withS. Enteritidis, and intestinal gene expression was measured at 1 or 7 days postinfection (p.i.) (5 or 11 days of age). Intestinal expression of innate immune mRNA transcripts was analyzed by quantitative real-time PCR (qRT-PCR). Analysis of relative mRNA expression showed that a BT peptide-supplemented diet did not directly induce the transcription of proinflammatory cytokine, inflammatory chemokine, type I/II interferon (IFN), or TLR mRNA in chicken cecum. However, feeding the BT peptide-supplemented diet primed cecal tissue for increased (P≤ 0.05) transcription of TLR4, TLR15, and TLR21 upon infection withS. Enteritidis on days 1 and 7 p.i. Likewise, feeding the BT peptides primed the cecal tissue for increased transcription of proinflammatory cytokines (interleukin 1β [IL-1β], IL-6, IL-18, type I and II IFNs) and inflammatory chemokine (CxCLi2) in response toS. Enteritidis infection 1 and 7 days p.i. compared to the chickens fed the basal diet. These small cationic peptides may prove useful as alternatives to antibiotics as local immune modulators in neonatal poultry by providing prophylactic protection againstSalmonellainfections.
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Berkovich, A., M. C. O'Keefe, P. Hensley, and L. Caporale. "Effect of N-methylation on the modulation by synthetic peptides of the activity of the complement-factor-B-derived serine proteinase CVFBb." Biochemical Journal 270, no. 2 (September 1, 1990): 531–37. http://dx.doi.org/10.1042/bj2700531.
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Although they share the active-site catalytic triad of less-specific enzymes such as trypsin and chymotrypsin, the serine proteinases of the complement and coagulation cascades each cleave a highly restricted set of substrates. Peptides with sequences similar to that at which C3 is cleaved by the alternative-pathway complement proteinase CVFBb were synthesized by solid-phase methodology and examined for their effects on the activity of this enzyme as measured by three different types of assays. It was found that a peptide methylated at the scissile bond was a far more effective inhibitor of the cleavage of the protein substrate C5 and of the lysis of guinea-pig erythrocytes by the alternative pathway than was the equivalent unmethylated peptide. Whereas the unmethylated peptide inhibited cleavage of the peptide substrate, the methylated peptide actually stimulated cleavage in this assay. This stimulation was found to be due to a 2.8-fold increase in kcat; the dissociation constant for the substrate was not altered significantly. One model consistent with this behaviour is that the binding of the activator peptide in the extended substrate-recognition region stabilizes a catalytically more active conformation of the active site. A small peptide substrate may have access to such an activated active site, whereas the larger substrate, C5, may be excluded from the site. These results demonstrate that the observed effect of a given compound on activity of an enzyme with an extended substrate-recognition region may depend upon the substrate.
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Rehfeld, Jens F. "Premises for Cholecystokinin and Gastrin Peptides in Diabetes Therapy." Clinical Medicine Insights: Endocrinology and Diabetes 12 (January 2019): 117955141988360. http://dx.doi.org/10.1177/1179551419883608.
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Gastrin and cholecystokinin (CCK) are classical gastrointestinal peptide hormones. Their biogenesis, structures, and intestinal secretory patterns are well-known with the striking feature that their receptor-bound ‘active sites’ are highly homologous and that this structure is conserved for more than 500 million years during evolution. Consequently, gastrin and CCK are agonists for the same receptor (the CCK2 receptor). But in addition, tyrosyl O-sulphated CCK are also bound to the specific CCK1 receptor. The receptors are widely expressed in the body, including pancreatic islet-cell membranes. Moreover, CCK and gastrin peptides are at various developmental stages and diseases expressed in pancreatic islets; also in human islets. Accordingly, bioactive gastrin and CCK peptides stimulate islet-cell growth as well as insulin and glucagon secretion. In view of their insulinotropic effects, gastrin and CCK peptides have come into focus as drug targets, either alone or in combination with other insulinotropic gut hormones or growth factors. So far, modified CCK and gastrin peptides are being examined as potential drugs for therapy of type 1 as well as type 2 diabetes mellitus.
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Kovačević, Monika, Mojca Čakić Semenčić, Kristina Radošević, Krešimir Molčanov, Sunčica Roca, Lucija Šimunović, Ivan Kodrin, and Lidija Barišić. "Conformational Preferences and Antiproliferative Activity of Peptidomimetics Containing Methyl 1′-Aminoferrocene-1-carboxylate and Turn-Forming Homo- and Heterochiral Pro-Ala Motifs." International Journal of Molecular Sciences 22, no. 24 (December 16, 2021): 13532. http://dx.doi.org/10.3390/ijms222413532.
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The concept of peptidomimetics is based on structural modifications of natural peptides that aim not only to mimic their 3D shape and biological function, but also to reduce their limitations. The peptidomimetic approach is used in medicinal chemistry to develop drug-like compounds that are more active and selective than natural peptides and have fewer side effects. One of the synthetic strategies for obtaining peptidomimetics involves mimicking peptide α-helices, β-sheets or turns. Turns are usually located on the protein surface where they interact with various receptors and are therefore involved in numerous biological events. Among the various synthetic tools for turn mimetic design reported so far, our group uses an approach based on the insertion of different ferrocene templates into the peptide backbone that both induce turn formation and reduce conformational flexibility. Here, we conjugated methyl 1′-aminoferrocene-carboxylate with homo- and heterochiral Pro-Ala dipeptides to investigate the turn formation potential and antiproliferative properties of the resulting peptidomimetics 2–5. Detailed spectroscopic (IR, NMR, CD), X-ray and DFT studies showed that the heterochiral conjugates 2 and 3 were more suitable for the formation of β-turns. Cell viability study, clonogenic assay and cell death analysis showed the highest biological potential of homochiral peptide 4.
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Vakili, Alireza, Mohsen Danesh Mesgaran, Reza Valizadeh, Alireza Heravi Moussavi, Mohammad Reza Nassiry, and Ali Hosseinkhani. "Ruminal peptide and ammonia nitrogen concentrations in steers fed diets with different concentrate to lucerne hay ratios." Proceedings of the British Society of Animal Science 2007 (April 2007): 214. http://dx.doi.org/10.1017/s1752756200021177.
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In ruminants, as much as 50% of the dietary crude protein can be converted to ammonia by ruminal microorganisms. A part of ammonia can be utilized as a bacterial nitrogen source; however, rates of ammonia production often exceed rates of ammonia utilization. Peptides are intermediates in the conversion of ingested protein to ammonia in the rumen and their accumulation depends upon the nature of diet (Mesgaran & Parker, 1995). The objective of the present experiment was to investigate the effect of diets differing in concentrate: lucerne hay ratios on the ruminal pH, ammonia-nitrogen concentration and ruminal peptide nitrogen concentration in Holstein steers.
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Sonklin, Chanikan, Natta Laohakunjit, and Orapin Kerdchoechuen. "Assessment of antioxidant properties of membrane ultrafiltration peptides from mungbean meal protein hydrolysates." PeerJ 6 (July 27, 2018): e5337. http://dx.doi.org/10.7717/peerj.5337.
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Background Bioactive peptides can prevent damage associated with oxidative stress in humans when consumed regularly. Recently, peptides have attracted immense interest because of their beneficial functional properties, safety and little or no side effects when used at high concentration. Most antioxidant peptides are small in size, less than 1 kDa, and contains a high proportion of hydrophobic amino acid. Particularly, tyrosine, leucine, alanine, isoleucine, valine, lysine, phenyalanine, cysteine, methionine and histidine in peptide chain exhibited high antioxidant activity. Mungbean meal protein (MMP) is highly abundant in hydrophobic amino acids. It indicated that MMP might be a good source of antioxidants. Therefore, the objectives were to optimize the conditions used to generate mungbean meal protein hydrolysate (MMPH) with antioxidant activity from bromelain and to investigate the antioxidant activities of different molecular weight (MW) peptide fraction. Methods Response Surface Methodology (RSM) was used for screening of the optimal conditions to produce MMPH. After that MMPH was fractionated using ultrafiltration membranes with different MW distributions. Crude-MMPH and four fractions were investigated for five antioxidant activities: 2,2,1-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, superoxide, ferric reducing antioxidant power (FRAP) and metal ion chelation activity. Results The optimal condition to produce the MMPH was 15% (w/w) of bromelain and hydrolysis time for 12 h which showed the greatest DPPH and ABTS radical scavenging activity. After mungbean protein from optimal condition was separated based on different molecular weight, the DPPH radical scavenging activity was the highest for the F4 (less than 1 kDa) peptide fraction. Metal ion chelating activity was generally weak, except for the F4 that had a value of 43.94% at a protein concentration of 5 mg/mL. The F4 also exhibited high hydroxyl and superoxide activities (54 and 65.1%), but moderate activity for ferric reducing antioxidant power (0.102 mmole Fe2+/g protein) compared to other peptide fractions and crude-MMPH. Molecular weight and amino acid were the main factors that determined the antioxidant activities of these peptide fractions. Results indicated that F4 had strong antioxidant potentials. Discussion The lowest MW fraction (less than 1 kDa) contributed to the highest DPPH, superoxide, hydroxyl and metal chelation activity because influence of low MW and high content of hydrophobic amino acid in peptide chain. Results from this study indicated that MMPH peptides donate protons to free radicals because they had significantly high DPPH value compared to superoxide, hydroxyl and FRAP, which reactions were electron donation. Moreover, MMPH peptides had the ability to inhibit transition metal ions because of highly abundant glutamic acid and aspartic acid in peptide chain.
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Panigrahi, Sunil K., Kana Meece, and Sharon L. Wardlaw. "Effects of Naltrexone on Energy Balance and Hypothalamic Melanocortin Peptides in Male Mice Fed a High-Fat Diet." Journal of the Endocrine Society 3, no. 3 (January 28, 2019): 590–601. http://dx.doi.org/10.1210/js.2018-00379.
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Abstract The hypothalamic melanocortin system composed of proopiomelanocortin (POMC) and agouti-related protein (AgRP) neurons plays a key role in maintaining energy homeostasis. The POMC-derived peptides, α-MSH and β-EP, have distinct roles in this process. α-MSH inhibits food intake, whereas β-EP, an endogenous opioid, can inhibit POMC neurons and stimulate food intake. A mouse model was used to examine the effects of opioid antagonism with naltrexone (NTX) on Pomc and Agrp gene expression and POMC peptide processing in the hypothalamus in conjunction with changes in energy balance. There were clear stimulatory effects of NTX on hypothalamic Pomc in mice receiving low- and high-fat diets, yet only transient decreases in food intake and body weight gain were noted. The effects on Pomc expression were accompanied by an increase in POMC prohormone levels and a decrease in levels of the processed peptides α-MSH and β-EP. Arcuate expression of the POMC processing enzymes Pcsk1, Pcsk2, and Cpe was not altered by NTX, but expression of Prcp, an enzyme that inactivates α-MSH, increased after NTX exposure. NTX exposure also stimulated hypothalamic Agrp expression, but the effects of NTX on energy balance were not enhanced in Agrp-null mice. Despite clear stimulatory effects of NTX on Pomc expression in the hypothalamus, only modest transient decreases in food intake and body weight were seen. Effects of NTX on POMC processing, and possibly α-MSH inactivation, as well as stimulatory effects on AgRP neurons could mitigate the effects of NTX on energy balance.
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Morin, A., B. Charley, A. Petit, and L. Chedid. "Effets protecteurs des muramyl peptides vis-a-vis d'infections virales expérimentales." Médecine et Maladies Infectieuses 15, no. 5 (May 1985): 298. http://dx.doi.org/10.1016/s0399-077x(85)80126-8.
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Tavares, Eva, Rosario Maldonado, and Francisco J. Miñano. "Aminoprocalcitonin-mediated suppression of feeding involves the hypothalamic melanocortin system." American Journal of Physiology-Endocrinology and Metabolism 304, no. 12 (June 15, 2013): E1251—E1262. http://dx.doi.org/10.1152/ajpendo.00590.2012.
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Aminoprocalcitonin (N-PCT), a neuroendocrine peptide encoded by the calcitonin-I (CALC-I) gene, suppresses food intake when administered centrally in rats. However, the neural pathways underlying this effect remain unclear. N-PCT and calcitonin receptors (CT-R) have been identified in hypothalamic regions involved in energy homeostasis, including the arcuate nucleus (ARC). Here, we hypothesized an involvement of the hypothalamic ARC in mediating the anorexic effects of central N-PCT based on its content of peptidergic neurons involved in feeding and its expression of N-PCT and CT-R. Fasting strongly reduced expression of the N-PCT precursor gene CALC-I in the ARC, and central immunoneutralization of endogenous N-PCT increased food intake. Intracerebroventricular administration of N-PCT reduced food intake in fed and fasted rats, and its effect was attenuated by a neutralizing anti-N-PCT antibody. Immunohistochemistry for N-PCT showed that it is expressed in astrocytes and neurons in the ARC and is colocalized with anorexigenic proopiomelanocortin (POMC) neurons. Fasting reduced coexpression of N-PCT and POMC, and N-PCT administration activated hypothalamic neurons, including rostral POMC neurons. We also found that N-PCT stimulates POMC mRNA expression in fed and fasted rats, whereas it reduced the expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related peptide (AgRP) only in fasted rats in which those mRNAs are normally elevated. Finally, we showed that the melanocortin-3/4 receptor antagonist SHU 9119 attenuates the intake-suppressive effect of N-PCT. These data demonstrate that hypothalamic N-PCT is involved in control of energy balance and that its anorexigenic effects are mediated through the melanocortin system.
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Eken, Ahmet, Vivian Ortiz, and Jack R. Wands. "Ethanol Inhibits Antigen Presentation by Dendritic Cells." Clinical and Vaccine Immunology 18, no. 7 (May 11, 2011): 1157–66. http://dx.doi.org/10.1128/cvi.05029-11.
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ABSTRACTPrevious studies suggest that altered virus-specific T-cell responses observed during chronic ethanol exposure may be due to abnormal functioning of dendritic cells (DCs). Here we explored the effects of ethanol on exogenous antigen presentation by DCs. BALB/c, C57BL/6, and CBA/caj mice were fed ethanol or an isocaloric control diet for 8 weeks. The splenic DC population was expanded using an Flt3L expression plasmid via tail vein injection. DCs were purified and assessed for antigen presentation and processing and for peptide-major histocompatibility complex class I and II (MHCI and MHCII) formation on the cell surface. Interleukin-2 (IL-2) was measured as an indicator of antigen-specific T-cell activation by DCs in coculture. Antigen processing and peptide-MHCII complexes were evaluated by flow cytometry. We observed that ethanol not only suppressed allogeneic peptide presentation to T cells by DCs but also altered presentation of exogenous ovalbumin (OVA) peptide 323-339 to an OVA-specific DO11 T-cell line as well as to OVA-sensitized primary T cells. Smaller amounts of peptide-MHCII complexes were found on the DCs isolated from the spleens of ethanol-fed mice. In contrast to MHCII presentation, cross-presentation of exogenous OVA peptide via MHCI by DCs remained intact. More importantly, ethanol-exposed DCs had reduced B7-DC and enhanced ICOS-L (inhibitory) costimulatory molecule expression. Ethanol inhibits exogenous and allogeneic antigen presentation and affects the formation of peptide-MHCII complexes, as well as altering costimulatory molecule expression on the cell surface. Therefore, DC presentation of peptides in a favorable costimulatory protein environment is required to subsequently activate T cells and appears to be a critical target for the immunosuppressive effects of ethanol.
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Mercier, A. J., I. Orchard, and V. TeBrugge. "FMRFamide-like immunoreactivity in the crayfish nervous system." Journal of Experimental Biology 156, no. 1 (March 1, 1991): 519–38. http://dx.doi.org/10.1242/jeb.156.1.519.
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FMRFamide-like immunoreactivity (FLI) was detected in the nervous system of the crayfish Procambarus clarkii using an antiserum that recognizes extended RFamide peptides. Immunocytochemistry revealed FLI in neuronal somata, axons and varicose processes within the central nervous system. In the periphery, plexuses of immunoreactive varicosities were present in the pericardial organs (POs), in thoracic roots and on the hindgut. The hindgut plexus arose from 3–5 axons leaving the sixth abdominal ganglion (A6) via the intestinal nerve. The presence of FLI in these locations was confirmed by radioimmunoassay. In contrast, no FLI was detected in motor axons innervating exoskeletal muscles of the abdomen. The POs contained by far the largest amount of FLI of all tissues examined. The immunoreactive material was partially characterized by extraction and separation on two consecutive reversed-phase high performance liquid chromatography (RP-HPLC) columns. The largest amount of immunoreactivity on the second column co-eluted with a synthetic peptide, SDRNFLRFamide (F2), previously identified as one of two or more FMRFamide-related peptides contained in lobster POs. The immunoreactive fractions and peptide F2 elicited similar effects on isolated crayfish hearts; all increased the rate and amplitude of spontaneous cardiac contractions. As with the immunoreactivity, the highest level of bioactivity was contained in the fraction that co-eluted with F2. The results suggest that FMRFamide-related peptides act as neurohormones in crayfish and are likely to play roles in controlling circulation and defecation.
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Hothi, S. K., D. P. Randall, and M. A. Titheradge. "[Leu]enkephalin stimulates carbohydrate metabolism in isolated hepatocytes and kidney tubule fragments by interaction with angiotensin II receptors." Biochemical Journal 257, no. 3 (February 1, 1989): 705–10. http://dx.doi.org/10.1042/bj2570705.
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The possibility that the effects of [Leu]enkephalin in vitro on hepatic carbohydrate metabolism are mediated by interaction with angiotensin II receptors has been examined. Preincubation of hepatocytes with either the angiotensin II receptor antagonist [Sar1,Ile8]angiotensin II or 10 mM-dithiothreitol abolished the ability of both angiotensin II and [Leu]enkephalin to increase phosphorylase a in hepatocytes prepared from fed rats. Dithiothreitol had no effect on the stimulation of phosphorylase in the presence of glucagon or phenylephrine, although it also inhibited the response to vasopressin. [Leu]enkephalin displaced specifically bound 125I-labelled angiotensin II from hepatic plasma membranes over a concentration range of 10(-7)-10(-5) M. This correlated with the dose-response required to stimulate phosphorylase activity in intact hepatocytes and suggests that the effects of the opioid peptides on carbohydrate metabolism in liver are the result of cross-reactivity of the peptides with angiotensin II receptors. Addition of 10(-5) M-[Leu]enkephalin to isolated kidney tubule fragments stimulated gluconeogenesis from 5 mM-pyruvate, the magnitude of stimulation being comparable to that by either angiotensin II or adrenaline. This effect of the opioid peptide was also abolished by pretreatment of the tubules with [Sar1,Ile8]angiotensin II, suggesting that the ability of [Leu]enkephalin to interact with angiotensin II receptors is not restricted to the liver, but may occur in other tissues where both receptors occur together.
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Williams, Gareth, Helena M. Cardoso, Ying C. Lee, Joanna M. Ball, Mohammad A. Ghatei, Michael J. Stock, and Stephen R. Bloom. "Hypothalamic regulatory peptides in obese and lean Zucker rats." Clinical Science 80, no. 5 (May 1, 1991): 419–26. http://dx.doi.org/10.1042/cs0800419.
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1. Hypothalamic concentrations of nine peptides with experimental effects on energy balance were compared in obese (fa/fa) and lean (Fa/?) male Zucker rats. To determine whether any peptide differences between obese and lean rats might be due to the overweight condition per se, separate groups of obese rats were food-restricted to reduce their body weight to lean values. 2. Concentrations of neuromedin B, a bombesin-like peptide, in the central hypothalamus were significantly higher in obese than in lean rats. This difference was not affected in food-restricted obese rats. 3. Hypothalamic levels of neuropeptide Y, an extremely potent central appetite stimulant, were similar in lean and freely fed obese rats but central hypothalamic levels of neuropeptide Y rose significantly in food-restricted obese rats. 4. These findings suggest that disturbances in hypothalamic neuromedin B concentrations may be involved in the obesity syndrome of the fa/fa Zucker rat. Increased central hypothalamic levels of neuropeptide Y in food-restricted rats suggest that this peptide may help to defend body weight by stimulating eating after weight loss.
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Rivas-Urbina, Andrea, Anna Rull, Joile Aldana-Ramos, David Santos, Nuria Puig, Nuria Farre-Cabrerizo, Sonia Benitez, et al. "Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice." Biomolecules 10, no. 6 (May 29, 2020): 829. http://dx.doi.org/10.3390/biom10060829.
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Mimetic peptides are potential therapeutic agents for atherosclerosis. d-[113–122]apolipoprotein (apo) J (d-[113–122]apoJ) is a 10-residue peptide that is predicted to form a class G* amphipathic helix 6 from apoJ; it shows anti-inflammatory and anti-atherogenic properties. In the present study, we analyzed the effect of d-[113–122]apoJ in low-density lipoprotein receptor knockout mice(LDLR-KO) on the development of atherosclerosis and lipoprotein function. Fifteen-week-old female LDLR-KO mice fed an atherogenic Western-type diet were treated for eight weeks with d-[113–122]apoJ peptide, a scrambled peptide, or vehicle. Peptides were administered subcutaneously three days per week (200 µg in 100 µL of saline). After euthanasia, blood and hearts were collected and the aortic arch was analyzed for the presence of atherosclerotic lesions. Lipoproteins were isolated and their composition and functionality were studied. The extent of atherosclerotic lesions was 43% lower with d-[113–122]apoJ treatment than with the vehicle or scramble. The lipid profile was similar between groups, but the high-density lipoprotein (HDL) of d-[113–122]apoJ-treated mice had a higher antioxidant capacity and increased ability to promote cholesterol efflux than the control group. In addition, low-density lipoprotein (LDL) from d-[113–122]apoJ-treated mice was more resistant to induced aggregation and presented lower electronegativity than in mice treated with d-[113–122]apoJ. Our results demonstrate that the d-[113–122]apoJ peptide prevents the extent of atherosclerotic lesions, which could be partially explained by the improvement of lipoprotein functionality.