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Artykuły w czasopismach na temat "Photo-reactive Receptors"
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Zhong, Huijun, Dirk Rüsch i Stuart A. Forman. "Photo-activated Azi-Etomidate, a General Anesthetic Photolabel, Irreversibly Enhances Gating and Desensitization of γ-Aminobutyric Acid Type A Receptors". Anesthesiology 108, nr 1 (1.01.2008): 103–12. http://dx.doi.org/10.1097/01.anes.0000296074.33999.52.
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Background The general anesthetic etomidate acts via gamma-aminobutyric acid type A (GABA(A)) receptors, enhancing activation at low GABA and prolonging deactivation. Azi-etomidate is a photo-reactive etomidate derivative with similar pharmacological actions, which has been used to identify putative binding sites. The authors examine the irreversible effects of azi-etomidate photo-modification on functional GABA(A) receptors in cell membranes. Methods GABA(A) receptors (alpha1beta2gamma2L) were expressed in both Xenopus oocytes and human embryonic kidney cells exposed to 365 nm light-activated azi-etomidate with or without GABA, then extensively washed. Receptor-mediated chloride currents were measured using voltage clamp electrophysiology to assess the ratio of peak responses at 10 microm and 1 mm GABA (I10/I1000) and deactivation time course. Results After azi-etomidate photo-modification, I10/I1000 ratios were persistently enhanced and deactivation was prolonged, mimicking reversible azi-etomidate actions. Azi-etomidate and ultraviolet light were required to produce irreversible receptor modulation. Adding GABA during photo-modification greatly enhanced irreversible modulation. Azi-etomidate modification also dose-dependently reduced maximal GABA-activated currents, consistent with accumulation of permanently desensitized receptors. Excess etomidate during azi-etomidate photo-modification competitively reduced permanent desensitization. Persistent channel modulation was blocked by 320-fold excess etomidate but enhanced when 32-fold excess etomidate was present. Conclusions Azi-etomidate efficiently photo-modifies etomidate sites on GABA(A) receptors in intact cells, producing persistent functional changes that mimic its reversible effects. The results demonstrate sequential modification at more than one etomidate site per receptor. The sites display reciprocal positive cooperativity. In combination with focal photo-activation, azi-etomidate may prove useful for studies of anesthetic actions in neural circuits.
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Forman, Stuart A., i Huijun Zhong. "Irreversible modulation of GABAA receptors by azi-etomidate, a photo-reactive general anesthetic". International Congress Series 1283 (listopad 2005): 271–72. http://dx.doi.org/10.1016/j.ics.2005.06.081.
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Ye, Shixin, Caroline Köhrer, Thomas Huber, Manija Kazmi, Pallavi Sachdev, Elsa C. Y. Yan, Aditi Bhagat, Uttam L. RajBhandary i Thomas P. Sakmar. "Site-specific Incorporation of Keto Amino Acids into Functional G Protein-coupled Receptors Using Unnatural Amino Acid Mutagenesis". Journal of Biological Chemistry 283, nr 3 (8.11.2007): 1525–33. http://dx.doi.org/10.1074/jbc.m707355200.
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G protein-coupled receptors (GPCRs) are ubiquitous heptahelical transmembrane proteins involved in a wide variety of signaling pathways. The work described here on application of unnatural amino acid mutagenesis to two GPCRs, the chemokine receptor CCR5 (a major co-receptor for the human immunodeficiency virus) and rhodopsin (the visual photoreceptor), adds a new dimension to studies of GPCRs. We incorporated the unnatural amino acids p-acetyl-l-phenylalanine (Acp) and p-benzoyl-l-phenylalanine (Bzp) into CCR5 at high efficiency in mammalian cells to produce functional receptors harboring reactive keto groups at three specific positions. We obtained functional mutant CCR5, at levels up to ∼50% of wild type as judged by immunoblotting, cell surface expression, and ligand-dependent calcium flux. Rhodopsin containing Acp at three different sites was also purified in high yield (0.5–2 μg/107 cells) and reacted with fluorescein hydrazide in vitro to produce fluorescently labeled rhodopsin. The incorporation of reactive keto groups such as Acp or Bzp into GPCRs allows their reaction with different reagents to introduce a variety of spectroscopic and other probes. Bzp also provides the possibility of photo-cross-linking to identify precise sites of protein-protein interactions, including GPCR binding to G proteins and arrestins, and for understanding the molecular basis of ligand recognition by chemokine receptors.
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Ding, Haiyan, Ahmad Ali i Zhihui Cheng. "An Allelopathic Role for Garlic Root Exudates in the Regulation of Carbohydrate Metabolism in Cucumber in a Hydroponic Co-Culture System". Plants 9, nr 1 (27.12.2019): 45. http://dx.doi.org/10.3390/plants9010045.
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Garlic is considered to have a strong positive effect on the growth and yield of receptors under soil cultivation conditions. However, how this positive promotion is produced by changing the growth environment of the receptors or directly acting on the receptors is still not very clear. The direct influence of co-culturing with different quantities of garlic plants (the control 5, 10, 15, 20) on the growth and biochemical processes of cucumber plants was studied using a hydroponic co-culture system. Different numbers of garlic bulbs inhibited the growth of cucumber plants and increased the production and induction of reactive oxygen species, which accompanied the enhancement of lipid peroxidation and oxidative damage to cucumber. This allelopathic exposure further reduced the chlorophyll contents and photosynthesis rate, and consequently impaired the photosynthetic performance of photosystem II (PSII). Garlic root exudates increased the leaves’ carbohydrates accumulation, such as soluble sugar contents and sucrose levels by regulating the activities of metabolismic enzymes; however, no such accumulation was observed in the roots. Our results suggested that garlic root exudates can mediate negative plant–plant interactions and its phytotoxic influence on cucumber plants may have occurred through the application of oxidative stress, which consequently imbalanced the source-to-sink photo-assimilate flow.
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Borghese, Cecilia M., Hua-Yu L. Wang, Stanton F. McHardy, Robert O. Messing, James R. Trudell, R. Adron Harris i Edward J. Bertaccini. "Modulation of α1β3γ2 GABAA receptors expressed in X. laevis oocytes using a propofol photoswitch tethered to the transmembrane helix". Proceedings of the National Academy of Sciences 118, nr 8 (16.02.2021): e2008178118. http://dx.doi.org/10.1073/pnas.2008178118.
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Tethered photoswitches are molecules with two photo-dependent isomeric forms, each with different actions on their biological targets. They include reactive chemical groups capable of covalently binding to their target. Our aim was to develop a β-subunit-tethered propofol photoswitch (MAP20), as a tool to better study the mechanism of anesthesia through the GABAA α1β3γ2 receptor. We used short spacers between the tether (methanethiosulfonate), the photosensitive moiety (azobenzene), and the ligand (propofol), to allow a precise tethering adjacent to the putative propofol binding site at the β+α− interface of the receptor transmembrane helices (TMs). First, we used molecular modeling to identify possible tethering sites in β3TM3 and α1TM1, and then introduced cysteines in the candidate positions. Two mutant subunits [β3(M283C) and α1(V227C)] showed photomodulation of GABA responses after incubation with MAP20 and illumination with lights at specific wavelengths. The α1β3(M283C)γ2 receptor showed the greatest photomodulation, which decreased as GABA concentration increased. The location of the mutations that produced photomodulation confirmed that the propofol binding site is located in the β+α− interface close to the extracellular side of the transmembrane helices. Tethering the photoswitch to cysteines introduced in the positions homologous to β3M283 in two other subunits (α1W288 and γ2L298) also produced photomodulation, which was not entirely reversible, probably reflecting the different nature of each interface. The results are in agreement with a binding site in the β+α− interface for the anesthetic propofol.
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Gęgotek, Agnieszka, Anna Jastrząb, Iwona Jarocka-Karpowicz, Marta Muszyńska i Elżbieta Skrzydlewska. "The Effect of Sea Buckthorn (Hippophae rhamnoides L.) Seed Oil on UV-Induced Changes in Lipid Metabolism of Human Skin Cells". Antioxidants 7, nr 9 (23.08.2018): 110. http://dx.doi.org/10.3390/antiox7090110.
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Lipids and proteins of skin cells are the most exposed to harmful ultraviolet (UV) radiation contained in sunlight. There is a growing need for natural compounds that will protect these sensitive molecules from damage, without harmful side effects. The aim of this study was to investigate the effect of sea buckthorn seed oil on the redox balance and lipid metabolism in UV irradiated cells formed different skin layers to examine whether it had a protective effect. Human keratinocytes and fibroblasts were subjected to UVA (ultraviolet type A; 30 J/cm2 and 20 J/cm2) or UVB (ultraviolet type B; 60 mJ/cm2 and 200 mJ/cm2, respectively) radiation and treated with sea buckthorn seed oil (500 ng/mL), and the redox activity was estimated by reactive oxygen species (ROS) generation and enzymatic/non-enzymatic antioxidants activity/level (using electron spin resonance (ESR), high-performance liquid chromatography (HPLC), and spectrophotometry). Lipid metabolism was measured by the level of fatty acids, lipid peroxidation products, endocannabinoids and phospholipase A2 activity (GC/MS (gas chromatography/mass spectrometry), LC/MS (liquid chromatography/mass spectrometry), and spectrophotometry). Also, transcription factor Nrf2 (nuclear erythroid 2-related factor) and its activators/inhibitors, peroxisome proliferator-activated receptors (PPAR) and cannabinoid receptor levels were measured (Western blot). Sea buckthorn oil partially prevents UV-induced ROS generation and enhances the level of non-enzymatic antioxidants such as glutathione (GSH), thioredoxin (Trx) and vitamins E and A. Moreover, it stimulates the activity of Nrf2 leading to enhanced antioxidant enzyme activity. As a result, decreases in lipid peroxidation products (4-hydroxynonenal, 8-isoprostaglandin) and increases in the endocannabinoid receptor levels were observed. Moreover, sea buckthorn oil treatment enhanced the level of phospholipid and free fatty acids, while simultaneously decreasing the cannabinoid receptor expression in UV irradiated keratinocytes and fibroblasts. The main differences in sea buckthorn oil on various skin cell types was observed in the case of PPARs—in keratinocytes following UV radiation PPAR expression was decreased by sea buckthorn oil treatment, while in fibroblasts the reverse effect was observed, indicating an anti-inflammatory effect. With these results, sea buckthorn seed oil exhibited prevention of UV-induced disturbances in redox balance as well as lipid metabolism in skin fibroblasts and keratinocytes, which indicates it is a promising natural compound in skin photo-protection.
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Haro, Kurtis J., Marta Gomez-Nunez, Tao Dao, Deming Chau, Annie Won, Sindy Escobar-Alvarez, Victoriya Zakhaleva, Tatyana Korontsvit, David Gin i David A. Scheinberg. "Photo-Reactive and Non-Natural Amino Acid Epitopes of Human WT1 Enhance Immunogenicity and Allow Kinetic Study of Antigen Processing." Blood 110, nr 11 (16.11.2007): 2311. http://dx.doi.org/10.1182/blood.v110.11.2311.2311.
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Abstract Wilms tumor protein (WT1) is a transcription factor selectively over expressed in several types of leukemia and solid tumors, making it a promising potential target antigen for immunotherapy. Several open clinical trials use native or altered peptide sequences derived from the WT1 protein in order to overcome the weak immunogenicity of the self-antigen. Here we report a new strategy to circumvent tolerance by designing peptides that incorporate non-natural amino acids into the native sequence of WT1 peptides. Starting from the nonamer sequences WT1 187–195 and WT1 235–243, eight peptides containing natural amino acids and nine peptides in which different chemical modifications (fluorination, photo-reactive azido groups or benzophenone groups) were introduced at major histocompatibility complex (MHC) and T cell receptor binding positions, were synthesized. The new non-natural peptides could stabilize MHC class I molecules better than the native sequences and were also able to elicit strong specific T-cell responses. Photo-reactive peptides were additionally modified with biotin handles to allow streptavidin-biotin pull down and western blot analysis of kinetics of binding and catabolism. Upon UV irradiation, these peptides covalently bound to MHC molecules on the live cells; clearance of the peptide-MHC covalent complex occurred over 24 hours, consistent with the T2 thermo-stabilization data for the same peptide. Further catabolic studies may elucidate the important or novel cellular proteins involved in antigenic peptide processing and cross presentation and should aid in vaccine development. We are investigating whether covalent interaction with the MHC may lead to alterations in immune responses as well. T cells stimulated with one of the synthetic peptides (WT1J-W4WF) cross-reacted with the native WT1J sequence and were able to kill WT1 positive HLA-A0201 matched acute lymphoblastic leukemia cell lines. In conclusion, this study shows that peptides with non-natural amino acids can be successfully incorporated into T cell epitopes to provide increased immunogenicity and novel biological information.
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Railkar, Reema, Spencer Krane, Q. Quentin Li, Thomas Sanford, Peter L. Choyke, Hisataka Kobayashi i Piyush K. Agarwal. "Epidermal growth factor receptor (EGFR) targeted photoimmunotherapy (PIT) for the treatment of EGFR expressing bladder cancer." Journal of Clinical Oncology 35, nr 6_suppl (20.02.2017): 291. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.291.
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291 Background: There are limited treatment options for patients with non-muscle invasive bladder cancer (NMIBC) who fail intravesical bacillus Calmette-Guerin (BCG). The use of light as a means of therapy for bladder cancer (BC) has a long history but has been hampered by a lack of tumor specificity and toxicity. Monoclonal antibody (mAb)-conjugates represent an emerging therapeutic approach for malignancies that improves upon tumor specificity. The use of a mAb-photo-absorber (PA) conjugate is a more selective method of delivering light therapy and has been termed “photoimmunotherapy” (PIT). In this report, PIT is used to target the epidermal growth factor receptor (EGFR). EGFR is a good tumor-specific target as it is enriched in the basal molecular subtype of BC. In the present study, anti-EGFR antibody panitumumab (pan) was labeled with the PA, IRDye 700Dx (IR700), to create a pan IR700 mAb-PA conjugate which is activated by near-infrared radiation (NIR). Methods: BC tissue microarray (TMA) and BC cell lines were analyzed for expression of EGFR. Mechanism of PIT induced cell death was studied using proliferation assays, transmission electron microscopy (TEM), and production of reactive oxygen species. Finally, the in vivo effect was studied in xenografts. Results: EGFR staining of TMAs showed that while most BCs have expression of EGFR to some degree, squamous cell carcinomas (SCC) have the highest expression of EGFR. Pan IR700 activated by NIR light rapidly killed UMUC-5 cells, a bladder SCC line. Pan alone, pan IR700 without NIR, or NIR alone had no effect on cells. TEM demonstrated that cell death is due to necrosis. Singlet oxygen species contributed towards cell death. NIR-PIT with pan IR700 reduced growth compared to only pan IR700 treated UMUC-5 xenograft tumors. Conclusions: PIT is a new targeted treatment for BC. Our data demonstrate that pan IR700-induced PIT selectively kills EGFR-expressing bladder cancer cells in vitro and in vivo and hence warrants further studies in orthotopic models and in patients. We suspect that EGFR-directed therapy with PIT is a viable strategy for the basal molecular subtype of BC and will be testing this hypothesis in the future.
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Naser, Hawraa A., Nisreen J. Mohammed i Rana A. Ghaleb. "Photodynamic therapy of cancer cells using folate conjugated gold nanoparticles as a new nanoplatform for targeted cancer therapy". International journal of health sciences, 6.07.2022, 2390–400. http://dx.doi.org/10.53730/ijhs.v6ns6.10420.
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Photodynamic therapy works through photo activation of a specific photosensitizer in a tumor in the presence of oxygen. PDT is widely applied in oncology to treat various cancers as it has a minimally invasive procedure and high selectivity, does not interfere with other treatments, and can be repeated as needed. A large amount of reactive oxygen species (ROS) and singlet oxygen is generated in a cancer cell during PDT, which destroys the tumor effectively. In this study, explained utilization of gold nanoparticles as a photosensitizer in photodynamic therapy of primary liver cancer and colorectal cancer that showed gold NPs exerted cytotoxic effects on cancer cells in dose dependent manner. In this study also used folic acid (a water-soluble vitamin) as ligand to increase targeting of nanoparticles to cancer cells were tumor cells over-expressing folate receptors for their rapid proliferation. The results showed that the folic acid conjugated Au NPs exerted a significant cytotoxic effect on cancer cells (decrease in cells viability) (p˂0.001) and upon irradiations the effects also enhanced significantly comparing with gold nanoparticles alone.
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Ghosh, Ria, Susmita Mondal, Dipanjan Mukherjee, Aniruddha Adhikari, Maitree Bhattacharyya i Samir Kumar Pal. "Inorganic-Organic Synergy in Nano-hybrids makes a New Class of Drug with Targeted Delivery: Glutamate Functionalization of Iron Nanoparticles for Potential Bone Marrow Delivery and X-ray Dynamic Therapy". Current Drug Delivery 19 (28.03.2022). http://dx.doi.org/10.2174/1567201819666220328142620.
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Abstract: The direct delivery of therapeutic molecules is generally inefficient and has several problems. Hence, nano medicines with targeted and controlled delivery applications have been an exciting field of research for the past decade. In this regard, the adjustable properties of inorganic nanoparticles like particle size distribution, ability to change the targeting ligand to have a higher affinity towards the pathologic cell, and controlled delivery properties have made it indispensable for targeted drug delivery applications. Changing the ligand on the surface of the inorganic nanoparticle can direct different therapeutic molecules to different organs like the liver, spleen, kidney, bone, and even brain. However, while the other targeted nano medicines are well-reported targeting of therapeutics to bone marrow cells is sparse in the literature. Hence, the administration of therapeutics for bone-related disorders like bone metastases leads to several problems like severe systemic toxicity and suboptimal efficacy. In this direction, we have shown our successful effort to functionalise a model inorganic nanoparticle (Fe2O3) by glutamate ligand which is reported to have a high affinity towards the NMDA receptors of the bone cells. We have performed spectroscopic studies to characterize the nano-hybrid. We have shown that the cargo or the Fe2O3 nanoparticle possesses the ability to generate photo-induced reactive oxygen species (ROS), thereby leading to a therapeutic opportunity for bone metastases. In addition, the nanoparticle also possesses the ability to generate enhanced ROS on X-ray irradiation, which may provide a new strategy for bone metastases and cancer therapy. Also, this paper reviews the advancement in the drug delivery applications of inorganic nanoparticles and highlights the crosstalk between the inorganic nanoparticles with the conjugated targeting ligand for efficient delivery applications.
Części książek na temat "Photo-reactive Receptors"
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Ambrosius, D., S. Bala-Mohan, C. Behrendt, K. Schäfer, A. Schüttler i D. Brandenburg. "NEW PHOTO-REACTIVE DERIVATIVES OF INSULIN FOR AFFINITY-LABELLING OF THE INSULIN RECEPTOR". W Porto Carras, Chalkidiki, Greece, Aug. 31–Sept. 5, 1986, redaktor Dimitrios Theodoropoulos, 521–24. Berlin, Boston: De Gruyter, 1987. http://dx.doi.org/10.1515/9783110864243-122.
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