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1
Bonen, Arend, Miriam Heynen, and Hideo Hatta. "Distribution of monocarboxylate transporters MCT1-MCT8 in rat tissues and human skeletal muscle." Applied Physiology, Nutrition, and Metabolism 31, no. 1 (February 1, 2006): 31–39. http://dx.doi.org/10.1139/h05-002.
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In the past decade, a family of monocarboxylate transporters (MCTs) have been identified that can potentially transport lactate, pyruvate, ketone bodies, and branched-chain ketoacids. Currently, 14 such MCTs are known. However, many orphan transporters exist that have transport capacities that remain to be determined. In addition, the tissue distribution of many of these MCTs is not well defined. Such a cataloging can, at times, begin to suggest the metabolic role of a particular MCT. Recently, a number of antibodies against selected MCTs (MCT1, -2, -4, and -5 to -8) have become commercially available. Therefore, we examined the protein expression of these MCTs in a large number of rat tissues (heart, skeletal muscle, skin, brain, testes, vas deferens, adipose tissue, liver, kidney, spleen, and pancreas), as well as in human skeletal muscle. Unexpectedly, many tissues coexpressed 4-5 MCTs. In particular, in rat skeletal muscle MCT1, MCT2, MCT4, MCT5, and MCT6 were observed. In human muscle, these same MCTs were present. We also observed a pronounced MCT7 signal in human muscle, whereas a very faint signal occurred for MCT8. In rat heart, which is an important metabolic sink for lactate, we confirmed that MCT1 and -2 were expressed. In addition, MCT6 and -8 were also prominently expressed in this tissue, although it is known that MCT8 does not transport aromatic amino acids or lactate. This catalog of MCTs in skeletal muscle and other tissues has revealed an unexpected complexity of coexpression, which makes it difficult to associate changes in monocarboxylate transport with the expression of a particular MCT. The differences in transport kinetics for lactate and pyruvate are only known for MCT1, -2 and -4. Transport kinetics remain to be established for many other MCTs. In conclusion, this study suggests that in skeletal muscle, as well as other tissues, lactate and pyruvate transport rates may not only involve MCT1 and -4, as other monocarboxylate transporters are also expressed in rat (MCT2, -5, -6) and human skeletal muscle (MCT2, -5, -6, -7).Key words: muscle, lactate, pyruvate, human, rat.
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Becker, Helen M., Nilufar Mohebbi, Angelica Perna, Vadivel Ganapathy, Giovambattista Capasso, and Carsten A. Wagner. "Localization of members of MCT monocarboxylate transporter family Slc16 in the kidney and regulation during metabolic acidosis." American Journal of Physiology-Renal Physiology 299, no. 1 (July 2010): F141—F154. http://dx.doi.org/10.1152/ajprenal.00488.2009.
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The monocarboxylate transporter family (MCT) comprises 14 members with distinct transport properties and tissue distribution. The kidney expresses several members of the MCT family, but only little is known about their exact distribution and function. Here, we investigated selected members of the MCT family in the mouse kidney. MCT1, MCT2, MCT7, and MCT8 localized to basolateral membranes of the epithelial cells lining the nephron. MCT1 and MCT8 were detected in proximal tubule cells whereas MCT7 and MCT2 were located in the thick ascending limb and the distal tubule. CD147, a β-subunit of MCT1 and MCT4, showed partially overlapping expression with MCT1 and MCT2. However, CD147 was also found in intercalated cells. We also detected SMCT1 and SMCT2, two Na+-dependent monocarboxylate cotransporters, on the luminal membrane of type A intercalated cells. Moreover, mice were given an acid load for 2 and 7 days. Acidotic animals showed a marked but transient increase in urinary lactate excretion. During acidosis, a downregulation of MCT1, MCT8, and SMCT2 was observed at the mRNA level, whereas MCT7 and SMCT1 showed increased mRNA abundance. Only MCT7 showed lower protein abundance whereas all other transporters remained unchanged. In summary, we describe for the first time the localization of various MCT transporters in mammalian kidney and demonstrate that metabolic acidosis induces a transient increase in urinary lactate excretion paralleled by lower MCT7 protein expression.
3
PRICE, T. Nigel, N. Vicky JACKSON, and P. Andrew HALESTRAP. "Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past." Biochemical Journal 329, no. 2 (January 15, 1998): 321–28. http://dx.doi.org/10.1042/bj3290321.
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Measurement of monocarboxylate transport kinetics in a range of cell types has provided strong circumstantial evidence for a family of monocarboxylate transporters (MCTs). Two mammalian MCT isoforms (MCT1 and MCT2) and a chicken isoform (REMP or MCT3) have already been cloned, sequenced and expressed, and another MCT-like sequence (XPCT) has been identified. Here we report the identification of new human MCT homologues in the database of expression sequence tags and the cloning and sequencing of four new full-length MCT-like sequences from human cDNA libraries, which we have denoted MCT3, MCT4, MCT5 and MCT6. Northern blotting revealed a unique tissue distribution for the expression of mRNA for each of the seven putative MCT isoforms (MCT1-MCT6 and XPCT). All sequences were predicted to have 12 transmembrane (TM) helical domains with a large intracellular loop between TM6 and TM7. Multiple sequence alignments showed identities ranging from 20% to 55%, with the greatest conservation in the predicted TM regions and more variation in the C-terminal than the N-terminal region. Searching of additional sequence databases identified candidate MCT homologues from the yeast Saccharomyces cerevisiae, the nematode worm Caenorhabditis elegans and the archaebacterium Sulfolobus solfataricus. Together these sequences constitute a new family of transporters with some strongly conserved sequence motifs, the possible functions of which are discussed.
4
Chidlow, Glyn, John P. M. Wood, Mark Graham, and Neville N. Osborne. "Expression of monocarboxylate transporters in rat ocular tissues." American Journal of Physiology-Cell Physiology 288, no. 2 (February 2005): C416—C428. http://dx.doi.org/10.1152/ajpcell.00037.2004.
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The aim of the present study was to determine the distribution of monocarboxylate transporter (MCT) subtypes 1-4 in the various structures of the rat eye by using a combination of conventional and real-time RT-PCR, immunoblotting, and immunohistochemistry. Retinal samples expressed mRNAs encoding all four MCTs. MCT1 immunoreactivity was observed in photoreceptor inner segments, Müller cells, retinal capillaries, and the two plexiform layers. MCT2 labeling was concentrated in the inner and outer plexiform layers. MCT4 immunolabeling was present only in the inner retina, particularly in putative Müller cells, and the plexiform layers. No MCT3 labeling could be observed. The retinal pigment epithelium (RPE)/choroid expressed high levels of MCT1 and MCT3 mRNAs but lower levels of MCT2 and MCT4 mRNAs. MCT1 was localized to the apical and MCT3 to the basal membrane of the RPE, whereas MCT2 staining was faint. Although MCT1-MCT4 mRNAs were all detectable in iris and ciliary body samples, only MCT1 and MCT2 proteins were expressed. These were present in the iris epithelium and the nonpigmented epithelium of the ciliary processes. MCT4 was localized to the smooth muscle lining of large vessels in the iris-ciliary body and choroid. In the cornea, MCT1 and MCT2 mRNAs and proteins were detectable in the epithelium and endothelium, whereas evidence was found for the presence of MCT4 and, to a lesser extent, MCT1 in the lens epithelium. The unique distribution of MCT subtypes in the eye is indicative of the pivotal role that these transporters play in the maintenance of ocular function.
5
Hadjiagapiou, Christos, Larry Schmidt, Pradeep K. Dudeja, Thomas J. Layden, and Krishnamurthy Ramaswamy. "Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate transporter 1." American Journal of Physiology-Gastrointestinal and Liver Physiology 279, no. 4 (October 1, 2000): G775—G780. http://dx.doi.org/10.1152/ajpgi.2000.279.4.g775.
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The short-chain fatty acid butyrate was readily taken up by Caco-2 cells. Transport exhibited saturation kinetics, was enhanced by low extracellular pH, and was Na+independent. Butyrate uptake was unaffected by DIDS; however, α-cyano-4-hydroxycinnamate and the butyrate analogs propionate and l-lactate significantly inhibited uptake. These results suggest that butyrate transport by Caco-2 cells is mediated by a transporter belonging to the monocarboxylate transporter family. We identified five isoforms of this transporter, MCT1, MCT3, MCT4, MCT5, and MCT6, in Caco-2 cells by PCR, and MCT1 was found to be the most abundant isoform by RNase protection assay. Transient transfection of MCT1, in the antisense orientation, resulted in significant inhibition of butyrate uptake. The cells fully recovered from this inhibition by 5 days after transfection. In conclusion, our data showed that the MCT1 transporter may play a major role in the transport of butyrate into Caco-2 cells.
6
Bruner, L. H., K. J. Johnson, G. O. Till, and R. A. Roth. "Complement is not involved in monocrotaline pyrrole-induced pulmonary injury." American Journal of Physiology-Heart and Circulatory Physiology 254, no. 2 (February 1, 1988): H258—H264. http://dx.doi.org/10.1152/ajpheart.1988.254.2.h258.
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Monocrotaline pyrrole (MCTP) causes pulmonary vascular injury, pulmonary hypertension, and right ventricular hypertrophy in rats. The mechanisms by which MCTP causes lung injury are not known. After treatment with a moderate dose of MCTP, several days pass before major lung injury is detected, thus suggesting that the damage is caused indirectly. Since activation of the complement system can cause lung injury, it was of interest to test whether complement activation may be important in lung injury due to MCTP. Accordingly, rats were given a single dose of MCTP (3.5 mg/kg iv), and serum hemolytic complement activity was measured at several times after rats were treated. Neutrophil aggregometry also was used to determine whether complement activation products could be detected in serum after MCTP was given in vivo. The effect of complement depletion on MCTP-induced pulmonary injury was tested by cotreating rats with purified cobra venom factor and MCTP. MCTP treatment did not cause detectable complement activation in vivo, and complement depletion did not protect rats from lung injury. The direct effect of MCTP on serum complement also was tested by exposing fresh rat serum to MCTP in vitro and measuring serum complement activity. MCTP decreased serum hemolytic complement activity in vitro, but it did not interfere with subsequent zymosan-induced activation of complement. These results suggest that complement does not play a role in the development of major lung injury that occurs several days after treatment of rats with MCTP.
7
Ganey, P. E., K. H. Sprugel, S. M. White, J. G. Wagner, and R. A. Roth. "Pulmonary hypertension due to monocrotaline pyrrole is reduced by moderate thrombocytopenia." American Journal of Physiology-Heart and Circulatory Physiology 255, no. 5 (November 1, 1988): H1165—H1172. http://dx.doi.org/10.1152/ajpheart.1988.255.5.h1165.
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To elucidate further the role of the platelet in the development of monocrotaline pyrrole (MCTP)-induced lung injury and pulmonary hypertension, MCTP-treated rats were made thrombocytopenic by cotreatment with an anti-rat platelet serum (PAS). Lung injury was assessed from increases in lung weight, lavage fluid protein concentration, and lactate dehydrogenase activity and from accumulation in lung tissue of 125I-labeled albumin. These indexes of injury were not different in MCTP-treated rats with normal or reduced platelet numbers at day 4,8, or 14. In MCTP-treated rats not receiving the PAS, pulmonary arterial pressure was elevated by day 8. However, pulmonary arterial pressure was the same as controls at both day 8 and day 14 in MCTP-treated rats made moderately thrombocytopenic by cotreatment with PAS. More marked reduction of platelet number abolished the protective effect of thrombocytopenia against pulmonary hypertension. In a separate series of experiments, treatment with antibodies to platelet-derived growth factor (PDGF), a potential mediator in the response to MCTP-induced injury, did not protect rats from the cardiopulmonary effects of MCTP. These data indicate that moderate reduction of the number of circulating platelets prevents MCTP-induced pulmonary hypertension but not MCTP-induced lung injury, suggesting that the platelet is involved in the pulmonary hypertensive response to MCTP-induced lung injury by unknown mechanisms.
8
Wagner, J. G., T. W. Petry, and R. A. Roth. "Characterization of monocrotaline pyrrole-induced DNA cross-linking in pulmonary artery endothelium." American Journal of Physiology-Lung Cellular and Molecular Physiology 264, no. 5 (May 1, 1993): L517—L522. http://dx.doi.org/10.1152/ajplung.1993.264.5.l517.
Full textAbstract:
Monocrotaline pyrrole (MCTP) is a putative, toxic metabolite of the pyrrolizidine alkaloid, monocrotaline (MCT). When given intravenously to rats, it produces a delayed and progressive injury to the vasculature of the lungs that results in pulmonary hypertension and right heart hypertrophy. Dysfunctional endothelium and vascular leak are early signs of overt injury to the lung. When administered to endothelial cell cultures, MCTP causes cell enlargement, delayed and progressive cytotoxicity, and inhibition of proliferation in surviving cells. MCTP is a bifunctional alkylating agent which binds to DNA and other macromolecules. To examine DNA-MCTP interactions in endothelium, MCTP-induced DNA cross-linking was characterized in cultures of porcine endothelial cells (PECs) derived from pulmonary artery. MCTP caused DNA cross-linking in a dose-dependent manner that was consistent with its ability to inhibit cell proliferation. PECs exposed to MCTP for 48 h developed cross-linking that was maximal at 2 days and remained significant through 10 days. Increasing the duration of PEC exposure to the medium to which MCTP had been added was associated with increased DNA cross-linking. These results indicate that MCTP causes DNA cross-linking, which may explain the inhibition of cell proliferation observed in pulmonary endothelial cells in vitro. The long-lasting nature of DNA cross-linking and its dose relatedness are consistent with the delayed and progressive effects of MCTP on endothelial cells in vitro and on pulmonary vasculature in vivo.
9
Ganey, P. E., and R. A. Roth. "Thromboxane does not mediate pulmonary vascular response to monocrotaline pyrrole." American Journal of Physiology-Heart and Circulatory Physiology 252, no. 4 (April 1, 1987): H743—H748. http://dx.doi.org/10.1152/ajpheart.1987.252.4.h743.
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The possible involvement of thromboxane (Tx) in the pulmonary hypertension caused by monocrotaline pyrrole (MCTP) administration to rats was investigated by pharmacological intervention of Tx synthesis and action. The cyclooxygenase inhibitor, ibuprofen, at doses that inhibited platelet function and suppressed plasma Tx levels, did not attenuate MCTP-induced right ventricular hypertrophy or increased lung weight. Dazmegrel, an inhibitor of Tx synthetase, did not affect the MCTP-induced increase in lung weight or the elevation of lactate dehydrogenase activity or protein concentration in bronchopulmonary lavage fluid, despite significant reduction of the plasma concentration of Tx. Dazmegrel also did not alter the vascular leak or right ventricular hypertrophy due to administration of MCTP to rats. Finally, the Tx receptor antagonist L-640,035 was tested using a dosing regimen that reduced the increase in right ventricular pressure caused by a stable endoperoxide analogue in MCTP-treated rats. Cotreatment with L-640,035 did not attenuate the increase in lung weight, lavage fluid lactate dehydrogenase activity or protein concentration, or the pulmonary hypertension caused by MCTP. These results indicate that interference with Tx synthesis or action does not attenuate the toxic effects of MCTP and suggest that Tx is not necessary for the cardiopulmonary response to MCTP.
10
Hoorn, C. M., and R. A. Roth. "Monocrotaline pyrrole alters DNA, RNA and protein synthesis in pulmonary artery endothelial cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 262, no. 6 (June 1, 1992): L740—L747. http://dx.doi.org/10.1152/ajplung.1992.262.6.l740.
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Administration of monocrotaline pyrrole (MCTP) to animals results in pulmonary vascular injury. Pulmonary vascular endothelium is a likely target for this pneumotoxicant. Cultured porcine pulmonary artery endothelial cells (PECs) treated with MCTP remain viable but are unable to divide and exhibit an altered morphology. Such responses raise a question about the extent to which affected cells carry out normal functions such as RNA and protein synthesis. Accordingly, the cellular activity of MCTP-treated PECs was examined in this study. PECs were treated with a single administration of MCTP or vehicle, and determinations of cell number, protein, and DNA content were made at times up to 7 days posttreatment. DNA, RNA, and protein synthesis were quantified by incorporation of [3H]thymidine, [3H]uridine, and [3H]leucine, respectively. Increases in cell number that occurred with time in the control cells were reduced in MCTP-treated cells. At 7 days posttreatment, both protein and DNA content increased above control levels. Synthesis of DNA, RNA, and protein continued in all treatment groups throughout the posttreatment period, but cells treated with high concentrations of MCTP showed less synthetic activity than controls during the initial 48 h posttreatment. By 7 days, MCTP-treated cells were producing significantly more DNA, RNA, and protein. These results indicate that cells treated with MCTP continue to synthesize DNA, resulting in an increased DNA content. In addition, treated cells continue to synthesize RNA and translate RNA into protein. Thus, cellular activity is maintained but altered substantially by MCTP exposure.
11
Reindel, J. F., C. M. Hoorn, J. G. Wagner, and R. A. Roth. "Comparison of response of bovine and porcine pulmonary arterial endothelial cells to monocrotaline pyrrole." American Journal of Physiology-Lung Cellular and Molecular Physiology 261, no. 6 (December 1, 1991): L406—L414. http://dx.doi.org/10.1152/ajplung.1991.261.6.l406.
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Monocrotaline (MCT)-induced vascular injury in liver and lung may be caused by interaction of MCT metabolites such as monocrotaline pyrrole (MCTP) with vascular cells. Responses of bovine and porcine pulmonary artery endothelial cells (BECs and PECs, respectively) to a single administration of MCTP were compared. MCTP caused a delayed and progressive release of lactate dehydrogenase (LDH) activity from BECs and a gradual decrease in monolayer cellularity. Surviving cells became markedly hypertrophic. PECs were less sensitive to the cytolytic effects of MCTP, showing minimal cell detachment and little release of LDH activity. However, monolayer cellularity, as assessed by PEC enumeration, decreased in a dose-dependent manner. Hypertrophy of surviving PECs was less pronounced than in BECs. MCTP caused enhanced release of prostacyclin from monolayers of BECs and PECs exposed to 10 micrograms MCTP/ml, and concentrations of 0.5 microgram/ml or greater caused equivalent reduction in colony-forming efficiency in both cell types. In summary, whereas BECs were more susceptible to the cytolytic and hypertrophic effects of MCTP, BECs and PECs responded similarly with regard to prostacyclin release and were equally sensitive to the cytostatic effects of this compound.
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Hosie, A. H. F., D. Allaway, and P. S. Poole. "A Monocarboxylate Permease of Rhizobium leguminosarum Is the First Member of a New Subfamily of Transporters." Journal of Bacteriology 184, no. 19 (October 1, 2002): 5436–48. http://dx.doi.org/10.1128/jb.184.19.5436-5448.2002.
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ABSTRACT Amino acid transport by Rhizobium leguminosarum is dominated by two ABC transporters, the general amino acid permease (Aap) and the branched-chain amino acid permease (Bra). However, mutation of these transporters does not prevent this organism from utilizing alanine for growth. An R. leguminosarum permease (MctP) has been identified which is required for optimal growth on alanine as a sole carbon and nitrogen source. Characterization of MctP confirmed that it transports alanine (Km = 0.56 mM) and other monocarboxylates such as lactate and pyruvate (Km = 4.4 and 3.8 μM, respectively). Uptake inhibition studies indicate that propionate, butyrate, α-hydroxybutyrate, and acetate are also transported by MctP, with the apparent affinity for solutes demonstrating a preference for C3-monocarboxylates. MctP has significant sequence similarity to members of the sodium/solute symporter family. However, sequence comparisons suggest that it is the first characterized permease of a new subfamily of transporters. While transport via MctP was inhibited by CCCP, it was not apparently affected by the concentration of sodium. In contrast, glutamate uptake in R. leguminosarum by the Escherichia coli GltS system did require sodium, which suggests that MctP may be proton coupled. Uncharacterized members of this new subfamily have been identified in a broad taxonomic range of species, including proteobacteria of the β-subdivision, gram-positive bacteria, and archaea. A two-component sensor-regulator (MctSR), encoded by genes adjacent to mctP, is required for activation of mctP expression.
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Hogan, M. E., J. G. Wagner, K. L. Klomparens, and R. A. Roth. "Morphologic alterations in porcine endothelial cells by the plant toxin metabolite, monocrotaline pyrrole." Proceedings, annual meeting, Electron Microscopy Society of America 48, no. 3 (August 12, 1990): 822–23. http://dx.doi.org/10.1017/s0424820100161679.
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Animals treated with the pyrrolizidine alkaloid metabolite, monocrotaline pyrrole (MCTP), show a progressive pulmonary hypertension associated with interstitial edema and smooth muscle thickening of muscular vessels in the lung. To determine what effect the blood borne toxin has on the endothelium, primary tissue cultures were treated with MCTP and were examined using the scanning electron microscope.Porcine endothelial cells were isolated, cultured, then plated on tissue culture slides and Millipore filters. The effect of cell density was examined by plating at three different concentrations, the most dense (control cells) being confluent at time of fixation. Cells received no treatment, the vehicle (N,Ndimethylformamide), 5μg MCTP/ml or 50μg MCTP/ml 24 hours after plating and were allowed to grow for an additional four days.The most striking changes were cell hypertrophy and an alteration in the cell's plating character at a dose of 50μg MCTP/ml. Hypertrophy of the endothelial cells was evident at the 50μg MCTP/ml dose, at which the treated cells approached 4 to 5 times the size of the untreated cells.
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Ji, Yong Bing, Tie Hu Li, Qi Lang Lin, Chan Ging Fang, and Xiao Xian Wang. "Preparation of Mesophase Pitch from Coal Tar Pitch for C/C Composites." Key Engineering Materials 334-335 (March 2007): 165–68. http://dx.doi.org/10.4028/www.scientific.net/kem.334-335.165.
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Mesophase pitch (MPP) has a high carbon yield and excellent graphitizability, compared with commercial coal tar pitch (CTP), which make it suitable for the preparation of C/C composites. In this paper, two MPP were prepared by heat-treatment of two coal tar pitches (CTP and modified coal tar pitch (MCTP)) in the presence of nitrogen. Elemental analysis and FTIR were used to monitor the change of chemical structures of MPP transition from CTP and MCTP. The pyrolysis behaviors of CTP and MCTP were studied by means of thermal analysis (TG and DSC). The morphologies of MPP were inspected by optical microscope. The structures of the MPP were characterized by XRD. The results show that there are more alkyl functional groups existing in CTP and MCTP than in MPP, and MPP has a higher C/H ratio than CTP and MCTP, which indicate MPP formation predominantly polycondense aromatic and release the alkyl functional groups. An endothermic band due to volatilize light compounds around 290 °C, two exothermic peaks at 430°C and 490 °C were characteristic of polymerization reactions, exothermic peaks of MCTP are higher than that of CTP because the former has a higher reaction active for its more alkyl side chain. The optical texture of MPP from CTP is mosaics texture, while from the MCTP is flow domains texture. (002), (101) peaks of graphite occur on XRD patterns, the peaks of MPP from MCTP are higher and narrower than MPP from CTP, which indicates the former is more graphitizability than the latter.
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Lee, Jason, Reuben Reich, Fang Xu, and Pravin B. Sehgal. "Golgi, trafficking, and mitosis dysfunctions in pulmonary arterial endothelial cells exposed to monocrotaline pyrrole and NO scavenging." American Journal of Physiology-Lung Cellular and Molecular Physiology 297, no. 4 (October 2009): L715—L728. http://dx.doi.org/10.1152/ajplung.00086.2009.
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Although the administration of monocrotaline (MCT) into experimental animals is in widespread use today in investigations of pulmonary arterial hypertension (PAH), the underlying cellular and subcellular mechanisms that culminate in vascular remodeling are incompletely understood. Bovine pulmonary arterial endothelial cells (PAECs) in culture exposed to monocrotaline pyrrole (MCTP) develop “megalocytosis” 18–24 h later characterized by enlarged hyperploid cells with enlarged Golgi, mislocalization of endothelial nitric oxide synthase away from the plasma membrane, decreased cell-surface/caveolar nitric oxide (NO), and hypo- S-nitrosylation of caveolin-1, clathrin heavy chain, and N-ethylmaleimide-sensitive factor. We investigated whether MCTP did in fact affect functional intracellular trafficking. The NO scavenger (4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) and the NO donor diethylamine NONOate were used for comparison. Both MCTP and c-PTIO produced distinctive four- to fivefold enlarged PAECs within 24–48 h with markedly enlarged/dispersed Golgi, as visualized by immunostaining for the Golgi tethers/matrix proteins giantin, GM130, and p115. Live-cell uptake of the Golgi marker C5 ceramide revealed a compact juxtanuclear Golgi in untreated PAECs, brightly labeled enlarged circumnuclear Golgi after MCTP, but minimally labeled Golgi elements after c-PTIO. These Golgi changes were reduced by NONOate. After an initial inhibition during the first day, both MCTP and c-PTIO markedly enhanced anterograde secretion of soluble cargo (exogenous vector-expressed recombinant horseradish peroxidase) over the next 4 days. Live-cell internalization assays using fluorescently tagged ligands showed that both MCTP and c-PTIO inhibited the retrograde uptake of acetylated low-density lipoprotein, transferrin, and cholera toxin B. Moreover, MCTP, and to a variable extent c-PTIO, reduced the cell-surface density of all receptors assayed (LDLR, TfnR, BMPR, Tie-2, and PECAM-1/CD31). In an important distinction, c-PTIO enhanced mitosis in PAECs but MCTP inhibited mitosis, even that due to c-PTIO, despite markedly exaggerated Golgi dispersal. Taken together, these data define a broad-spectrum Golgi and subcellular trafficking dysfunction syndrome in endothelial cells exposed to MCTP or NO scavenging.
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Wood, J. I., K. L. Klomparens, C. M. Hoorn, R. A. Roth, and J. Reindel. "Effect of monocrotaline pyrrole on cultured cell cytoskeletons: An ultrastructural study." Proceedings, annual meeting, Electron Microscopy Society of America 49 (August 1991): 122–23. http://dx.doi.org/10.1017/s0424820100084910.
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The cytoskeleton (CS) is responsible for locomotion, intracellular motility and maintenance of cell structure. The system is composed of three major components: microfilaments, responsible for motility and cell structure, microtubules for organization and movement within the cell, and intermediate filaments, which may provide stability of intracellular contents.Monocrotaline (MCT) is a pyrrolizidine alkaloid plant toxin. When administered to rats, MCT is metabolized to monocrotaline pyrrole (MCTP) which induces lung injury and pulmonary hypertension. When administered to cultured pulmonary artery endothelial cells, MCTP causes progressive detachment, release of LDH, inhibition of cell proliferation, and distorted and enlarged nuclei. MCTP is a bifunctional alkylating agent that can crosslink DNA. We speculate that MCTP may also affect the cytoskeleton, resulting in inhibition of cell division.
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Mukhopadhyay, Somshuvra, Jason Lee, and Pravin B. Sehgal. "Depletion of the ATPase NSF from Golgi membranes with hypo-S-nitrosylation of vasorelevant proteins in endothelial cells exposed to monocrotaline pyrrole." American Journal of Physiology-Heart and Circulatory Physiology 295, no. 5 (November 2008): H1943—H1955. http://dx.doi.org/10.1152/ajpheart.00642.2008.
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Investigations of regulated S-nitrosylation and denitrosylation of vasorelevant proteins are a newly emergent area in vascular biology. We previously showed that monocrotaline pyrrole (MCTP)-induced megalocytosis of pulmonary arterial endothelial cells (PAECs), which underlies the development of pulmonary arterial hypertension, was associated with a Golgi blockade characterized by the trapping of diverse vesicle tethers, soluble N-ethylmaleimide-sensitive factor (NSF)-attachment protein receptors (SNAREs), and soluble NSF-attachment proteins (SNAPs) in the Golgi; reduced trafficking of caveolin-1 (cav-1) and endotheial nitric oxide (NO) synthase (eNOS) from the Golgi to the plasma membrane; and decreased caveolar NO. We have investigated whether NSF, the ATPase involved in all SNARE disassembly, might be the upstream target of MCTP and whether MCTP might regulate NSF by S-nitrosylation. Immunofluorescence microscopy and Golgi purification techniques revealed the discordant decrease of NSF by ∼50% in Golgi membranes after MCTP despite increases in α-SNAP, cav-1, eNOS, and syntaxin-6. The NO scavenger (4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide failed to affect the initiation or progression of MCTP megalocytosis despite a reduction of 4,5-diaminofluorescein diacetate fluorescence and inhibition of S-nitrosylation of eNOS as assayed using the biotin-switch method. Moreover, the latter assay not only revealed constitutive S-nitrosylation of NSF, eNOS, cav-1, and clathrin heavy chain (CHC) in PAECs but also a dramatic 70–95% decrease in the S-nitrosylation of NSF, eNOS, cav-1, and CHC after MCTP. These data point to depletion of NSF from Golgi membranes as a mechanism for Golgi blockade after MCTP and to denitrosylation of vasorelevant proteins as critical to the development of endothelial cell megalocytosis.
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Ovens, Matthew J., Christine Manoharan, Marieangela C. Wilson, Clarey M. Murray, and Andrew P. Halestrap. "The inhibition of monocarboxylate transporter 2 (MCT2) by AR-C155858 is modulated by the associated ancillary protein." Biochemical Journal 431, no. 2 (September 28, 2010): 217–25. http://dx.doi.org/10.1042/bj20100890.
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In mammalian cells, MCTs (monocarboxylate transporters) require association with an ancillary protein to enable plasma membrane expression of the active transporter. Basigin is the preferred binding partner for MCT1, MCT3 and MCT4, and embigin for MCT2. In rat and rabbit erythrocytes, MCT1 is associated with embigin and basigin respectively, but its sensitivity to inhibition by AR-C155858 was found to be identical. Using RT (reverse transcription)–PCR, we have shown that Xenopus laevis oocytes contain endogenous basigin, but not embigin. Co-expression of exogenous embigin was without effect on either the expression of MCT1 or its inhibition by AR-C155858. In contrast, expression of active MCT2 at the plasma membrane of oocytes was significantly enhanced by co-expression of exogenous embigin. This additional transport activity was insensitive to inhibition by AR-C155858 unlike that by MCT2 expressed with endogenous basigin that was potently inhibited by AR-C155858. Chimaeras and C-terminal truncations of MCT1 and MCT2 were also expressed in oocytes in the presence and absence of exogenous embigin. L-Lactate Km values for these constructs were determined and revealed that the TM (transmembrane) domains of an MCT, most probably TM7–TM12, but not the C-terminus, are the major determinants of L-lactate affinity, whereas the associated ancillary protein has little or no effect. Inhibitor titrations of lactate transport by these constructs indicated that embigin modulates MCT2 sensitivity to AR-C155858 through interactions with both the intracellular C-terminus and TMs 3 and 6 of MCT2. The C-terminus of MCT2 was found to be essential for its expression with endogenous basigin.
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HALESTRAP, Andrew P., and Nigel T. PRICE. "The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation." Biochemical Journal 343, no. 2 (October 8, 1999): 281–99. http://dx.doi.org/10.1042/bj3430281.
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Monocarboxylates such as lactate and pyruvate play a central role in cellular metabolism and metabolic communication between tissues. Essential to these roles is their rapid transport across the plasma membrane, which is catalysed by a recently identified family of proton-linked monocarboxylate transporters(MCTs). Nine MCT-related sequences have so far been identified in mammals, each having a different tissue distribution, whereas six related proteins can be recognized in Caenorhabditis elegansand 4 in Saccharomyces cerevisiae. Direct demonstration of proton-linked lactate and pyruvate transport has been demonstrated for mammalian MCT1-MCT4, but only for MCT1 and MCT2 have detailed analyses of substrate and inhibitor kinetics been described following heterologous expression in Xenopusoocytes. MCT1 is ubiquitously expressed, but is especially prominent in heart and red muscle, where it is up-regulated in response to increased work, suggesting a special role in lactic acid oxidation. By contrast, MCT4 is most evident in white muscle and other cells with a high glycolytic rate, such as tumour cells and white blood cells, suggesting it is expressed where lactic acid efflux predominates. MCT2 has a ten-fold higher affinity for substrates than MCT1 and MCT4 and is found in cells where rapid uptake at low substrate concentrations may be required, including the proximal kidney tubules, neurons and sperm tails. MCT3 is uniquely expressed in the retinal pigment epithelium. The mechanisms involved in regulating the expression of different MCT isoforms remain to be established. However, there is evidence for alternative splicing of the 5′- and 3′-untranslated regions and the use of alternative promoters for some isoforms. In addition, MCT1 and MCT4 have been shown to interact specifically with OX-47 (CD147), a member of the immunoglobulin superfamily with a single transmembrane helix. This interaction appears to assist MCT expression at the cell surface. There is still much work to be done to characterize the properties of the different isoforms and their regulation, which may have wide-ranging implications for health and disease. In the future it will be interesting to explore the linkage of genetic diseases to particular MCTs through their chromosomal location.
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HIDAYATSYAH, M. R., F. HANUM, and P. T. SUPRIYO. "PENJADWALAN KERETA PADA JALUR GANDA SECARA PERIODIK DENGAN BIAYA MINIMUM." Journal of Mathematics and Its Applications 10, no. 2 (December 1, 2011): 19. http://dx.doi.org/10.29244/jmap.10.2.19-30.
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Kereta merupakan alat transportasi massal yang banyak digunakan oleh masyarakat. Agar kebutuhan akan alat transportasi tersebut terpenuhi, dibutuhkan penjadwalan yang baik. Model penjadwalan kereta yang akan dibahas dalam karya ilmiah ini ialah MCSP (minimum cost scheduling problem) yaitu sebuah model penjadwalan kereta yang meminimumkan biaya operasional yang diformulasikan sebagai integer programming. MCSP memiliki dua bagian yaitu MCTP (minimum cost train problem) pada bagian pertama dan masalah penjadwalan pada bagian kedua. Pada bagian pertama, dilakukan pemilihan kereta yang tepat untuk rute tertentu dengan biaya minimum, sedangkan pada bagian kedua dilakukan penjadwalan berdasarkan kereta yang terpilih. Penjadwalan kereta dilakukan hanya untuk satu periode waktu dan secara periodik berlaku pula untuk periode waktu lainnya. Model ini diselesaikan menggunakan LINGO 11.0 dan hasil yang diperoleh berupa jadwal perjalanan kereta yang terpilih pada jalur tertentu dengan biaya operasional minimum.
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Benton, Carley R., Yuko Yoshida, James Lally, Xiao-Xia Han, Hideo Hatta, and Arend Bonen. "PGC-1α increases skeletal muscle lactate uptake by increasing the expression of MCT1 but not MCT2 or MCT4." Physiological Genomics 35, no. 1 (September 2008): 45–54. http://dx.doi.org/10.1152/physiolgenomics.90217.2008.
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We examined the relationship between PGC-1α protein; the monocarboxylate transporters MCT1, 2, and 4; and CD147 1) among six metabolically heterogeneous rat muscles, 2) in chronically stimulated red (RTA) and white tibialis (WTA) muscles (7 days), and 3) in RTA and WTA muscles transfected with PGC-1α-pcDNA plasmid in vivo. Among rat hindlimb muscles, there was a strong positive association between PGC-1α and MCT1 and CD147, and between MCT1 and CD147. A negative association was found between PGC-1α and MCT4, and CD147 and MCT4, while there was no relationship between PGC-1α or CD147 and MCT2. Transfecting PGC-1α-pcDNA plasmid into muscle increased PGC-1α protein (RTA +23%; WTA +25%) and induced the expression of MCT1 (RTA +16%; WTA +28%), but not MCT2 and MCT4. As a result of the PGC-1α-induced upregulation of MCT1 and its chaperone CD147 (+29%), there was a concomitant increase in the rate of lactate uptake (+20%). In chronically stimulated muscles, the following proteins were upregulated, PGC-1α in RTA (+26%) and WTA (+86%), MCT1 in RTA (+61%) and WTA (+180%), and CD147 in WTA (+106%). In contrast, MCT4 protein expression was not altered in either RTA or WTA muscles, while MCT2 protein expression was reduced in both RTA (−14%) and WTA (−10%). In these studies, whether comparing oxidative capacities among muscles or increasing their oxidative capacities by PGC-1α transfection and chronic muscle stimulation, there was a strong relationship between the expression of PGC-1α and MCT1, and PGC-1α and CD147 proteins. Thus, MCT1 and CD147 belong to the family of metabolic genes whose expression is regulated by PGC-1α in skeletal muscle.
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Muñoz-Bermejo, Laura, Sabina Barrios-Fernandez, Jorge Carlos-Vivas, María Mendoza-Muñoz, Raquel Pastor-Cisneros, Eugenio Merellano-Navarro, Konstantinos Gianikellis, and José Carmelo Adsuar. "Effectiveness of a 12-Week Multi-Component Training Program with and without Transcranial Direct-Current Stimulation (tDCS) on Balance to Prevent Falls in Community-Dwelling Older Adults: A Study Protocol." Biology 11, no. 2 (February 11, 2022): 290. http://dx.doi.org/10.3390/biology11020290.
Full textAbstract:
Approximately one-third of elderly people aged over 65 who live in the community experience falls every year, with the proportion increasing with age. Moreover, of those who fall, about half will fall again in the following year. The falls’ consequences include disability, morbidity, and mortality. Although many external and internal factors lead to falls, balance issues play a major role. Multi-component training programs (McTP) usually combine balance, strength, cardiorespiratory fitness, and flexibility, with studies reporting multiple benefits on the health-related quality of life. Halo Sport is a transcranial direct-current stimulation (tDCS) device with promising results for gait performance. This study aims to test the effectiveness of the introduction of a tCDS device to an McTP to prevent falls in older adults. The sample will consist of 46 people aged 65 years or older, randomly assigned to experimental (n = 23) and control (n = 23) groups. The experimental group will perform the McTP while wearing tDCS, and the control group will perform McTP without the device, for three sessions per week over 12 weeks. The main measures will provide information about (1) safety, (2) applicability, (3) balance, (4) number of falls, (5) physical fitness, (6) risk of falling, (7) fear of falling, (8) health-related quality of life, and (9) cognitive function. Among the practical implications of this program, it is intended to provide data on its safety and effectiveness to be implemented in different resources as a tool for the prevention of falls.
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Pinheiro, Céline, Rui M. Reis, Sara Ricardo, Adhemar Longatto-Filho, Fernando Schmitt, and Fátima Baltazar. "Expression of Monocarboxylate Transporters 1, 2, and 4 in Human Tumours and Their Association with CD147 and CD44." Journal of Biomedicine and Biotechnology 2010 (2010): 1–7. http://dx.doi.org/10.1155/2010/427694.
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Monocarboxylate transporters (MCTs) are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein.
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Sehgal, Pravin B., Somshuvra Mukhopadhyay, Fang Xu, Kirit Patel, and Mehul Shah. "Dysfunction of Golgi tethers, SNAREs, and SNAPs in monocrotaline-induced pulmonary hypertension." American Journal of Physiology-Lung Cellular and Molecular Physiology 292, no. 6 (June 2007): L1526—L1542. http://dx.doi.org/10.1152/ajplung.00463.2006.
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Monocrotaline (MCT)-induced pulmonary hypertension (PH) in the rat is a widely used experimental model. We have previously shown that MCT pyrrole (MCTP) produces loss of caveolin-1 (cav-1) and endothelial nitric oxide synthase from plasma membrane raft microdomains in pulmonary arterial endothelial cells (PAEC) with the trapping of these proteins in the Golgi organelle (the Golgi blockade hypothesis). In the present study, we investigated the mechanisms underlying this intracellular trafficking block in experiments in cell culture and in the MCT-treated rat. In cell culture, PAEC showed trapping of cav-1 in Golgi membranes as early as 6 h after exposure to MCTP. Phenotypic megalocytosis and a reduction in anterograde trafficking (assayed in terms of the secretion of horseradish peroxidase derived from exogenously transfected expression constructs) were evident within 12 h after MCTP. Cell fractionation and immunofluorescence techniques revealed the marked accumulation of diverse Golgi tethers, soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptors (SNAREs), and soluble NSF attachment proteins (SNAPs), which mediate membrane fusion during vesicular trafficking (GM130, p115, giantin, golgin 84, clathrin heavy chain, syntaxin-4, -6, Vti1a, Vti1b, GS15, GS27, GS28, SNAP23, and α-SNAP) in the enlarged/circumnuclear Golgi in MCTP-treated PAEC and A549 lung epithelial cells. Moreover, NSF, an ATPase required for the “disassembly” of SNARE complexes subsequent to membrane fusion, was increasingly sequestered in non-Golgi membranes. Immunofluorescence studies of lung tissue from MCT-treated rats confirmed enlargement of perinuclear Golgi elements in lung arterial endothelial and parenchymal cells as early as 4 days after MCT. Thus MCT-induced PH represents a disease state characterized by dysfunction of Golgi tethers, SNAREs, and SNAPs and of intracellular vesicular trafficking.
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Mukhopadhyay, Somshuvra, Fang Xu, and Pravin B. Sehgal. "Aberrant cytoplasmic sequestration of eNOS in endothelial cells after monocrotaline, hypoxia, and senescence: live-cell caveolar and cytoplasmic NO imaging." American Journal of Physiology-Heart and Circulatory Physiology 292, no. 3 (March 2007): H1373—H1389. http://dx.doi.org/10.1152/ajpheart.00990.2006.
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We previously reported the disruption of caveolae/rafts, dysfunction of Golgi tethers, N-ethylmaleimide-sensitive factor-attachment protein (SNAP) receptor proteins (SNAREs), and SNAPs, and inhibition of anterograde trafficking in endothelial cells in culture and rat lung exposed to monocrotaline pyrrole (MCTP) as a prelude to the development of pulmonary hypertension. We have now investigated 1) whether this trafficking block affects subcellular localization and function of endothelial nitric oxide (NO) synthase (eNOS) and 2) whether Golgi blockade and eNOS sequestration are observed after hypoxia and senescence. Immunofluorescence data revealed that MCTP-induced “megalocytosis” of pulmonary arterial endothelial cells (PAEC) was accompanied by a loss of eNOS from the plasma membrane, with increased accumulation in the cytoplasm. This cytoplasmic eNOS was sequestered in heterogeneous compartments and partially colocalized with Golgi and endoplasmic reticulum (ER) markers, caveolin-1, NOSTRIN, and ER Tracker, but not Lyso Tracker. Hypoxia and senescence also produced enlarged PAEC, with dysfunctional Golgi and loss of eNOS from the plasma membrane, with sequestration in the cytoplasm. Live-cell imaging of caveolar and cytoplasmic NO with 4,5-diaminofluorescein diacetate (DAF-2DA) as probe showed a marked loss of caveolar NO after MCTP, hypoxia, and senescence. Although ionomycin stimulated DAF-2DA fluorescence in control PAEC, this ionophore decreased DAF-2DA fluorescence in MCTP-treated and senescent PAEC, suggesting localization of eNOS in an aberrant cytoplasmic compartment that was readily discharged by Ca2+-induced exocytosis. Thus monocrotaline, hypoxia, and senescence produce a Golgi blockade in PAEC, leading to sequestration of eNOS away from its functional caveolar location and providing a mechanism for the often-reported reduction in pulmonary arterial NO levels in experimental pulmonary hypertension, despite sustained eNOS protein levels.
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Jansen, S., M. Pantaleon, and P. Kaye. "236.Differential expression of monocarboxylate cotransporter proteins in preimplantation embryos." Reproduction, Fertility and Development 16, no. 9 (2004): 236. http://dx.doi.org/10.1071/srb04abs236.
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During preimplantation development mouse embryos demonstrate a switch in substrate preference. Pyruvate consumption, high during the first few cleavage stages, declines as the morula develops to a blastocyst, when glucose becomes the preferred substrate. Whilst pyruvate utilisation has been well characterised, changes in the function and expression of pyruvate transporters during this crucial period remain unclear. Pyruvate, lactate and other monocarboxylates are transported across mammalian cell membranes via a specific H+-monocarboxylate cotransporter (MCT). Fourteen members of this family have been identified of which MCT1, MCT2 and MCT4 are well characterised. Although mRNA expression profiles are known during early mouse development (1,2), the specific roles of each protein isoform are unknown. In order to understand these, the expression pattern for each isoform and their cellular localisation during preimplantation development have been determined. Mouse embryos were freshly collected from superovulated Quackenbush mice at 24, 48, 72 and 96 h post-hCG and expression of MCT1, MCT2 and MCT4 analysed by confocal laser scanning immunohistochemistry. Our results confirm that all three MCT proteins are expressed in preimplantation embryos. Immunoreactivity for MCT1 and MCT2 appears diffuse throughout the cytoplasm of cleavage stage embryos. As development proceeds, MCT1 localised to the basolateral membranes of morulae and blastocysts, whilst stronger MCT2 expression was found on the apical trophectoderm as well as the inner cell mass. MCT4 immunoreactivity on the other hand is apparent at cell-cell contact sites in cleavage stage embryos and morulae, but it is not apparent in the blastocyst. The demonstration of different expression patterns for MCT1, MCT2 and MCT4 in mouse embryos implies specific functional roles for each in the critical regulation of H+, pyruvate and lactate transport during preimplantation development. (1) Harding EA, Day ML, Gibb CA, Johnson MH, Cook DI (1999) The activity of the H+-monocarboxylate cotransporter during pre-implantation development in the mouse. Eur. J. Physiol. 438, 397–404. (2) H�rubel F, El Mouatassim S, Gu�rin P, Frydman R, M�n�zo Y (2002) Genetic expression of monocarboxylate transporters during human and murine oocyte maturation and early embryonic development. Zygote 10, 175–181.
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Takimoto, Masaki, and Taku Hamada. "Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins." Journal of Applied Physiology 116, no. 9 (May 1, 2014): 1238–50. http://dx.doi.org/10.1152/japplphysiol.01288.2013.
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The brain is capable of oxidizing lactate and ketone bodies through monocarboxylate transporters (MCTs). We examined the protein expression of MCT1, MCT2, MCT4, glucose transporter 1 (GLUT1), and cytochrome- c oxidase subunit IV (COX IV) in the rat brain within 24 h after a single exercise session. Brain samples were obtained from sedentary controls and treadmill-exercised rats (20 m/min, 8% grade). Acute exercise resulted in an increase in lactate in the cortex, hippocampus, and hypothalamus, but not the brainstem, and an increase in β-hydroxybutyrate in the cortex alone. After a 2-h exercise session MCT1 increased in the cortex and hippocampus 5 h postexercise, and the effect lasted in the cortex for 24 h postexercise. MCT2 increased in the cortex and hypothalamus 5–24 h postexercise, whereas MCT2 increased in the hippocampus immediately after exercise, and remained elevated for 10 h postexercise. Regional upregulation of MCT2 after exercise was associated with increases in brain-derived neurotrophic factor and tyrosine-related kinase B proteins, but not insulin-like growth factor 1. MCT4 increased 5–10 h postexercise only in the hypothalamus, and was associated with increased hypoxia-inducible factor-1α expression. However, none of the MCT isoforms in the brainstem was affected by exercise. Whereas GLUT 1 in the cortex increased only at 18 h postexercise, COX IV in the hippocampus increased 10 h after exercise and remained elevated for 24 h postexercise. These results suggest that acute prolonged exercise induces the brain region-specific upregulation of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins.
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Zhang, Caixin, Pengbo Wang, Anaz Mohammed, Zhewen Zhou, Shuwen Zhang, Songshi Ni, and Zhiyuan Tang. "Function of Adipose-Derived Mesenchymal Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension through miR-191 via Regulation of BMPR2." BioMed Research International 2019 (April 16, 2019): 1–12. http://dx.doi.org/10.1155/2019/2858750.
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Pulmonary arterial hypertension (PAH) is a serious condition. However, prevailing therapeutic strategies are not effective enough to treat PAH. Therefore, finding an effective therapy is clearly warranted. Adipose-derived mesenchymal stem cells (ASCs) and ASCs-derived exosomes (ASCs-Exos) exert protective effects in PAH, but the underlying mechanism remains unclear. Using a coculture of ASCs and monocrotaline pyrrole (MCTP)-treated human pulmonary artery endothelial cells (HPAECs), we demonstrated that ASCs increased cell proliferation in MCTP-treated HPAECs. Results showed that ASCs-Exos improved proliferation of both control HPAECs and MCTP-treated HPAECs. In addition, by transfecting ASCs with antagomir we observed that low exosomal miR-191 expression inhibited HPAECs proliferation whereas the agomir improved. Similar results were observed in vivo using a monocrotaline (MCT)-induced PAH rat model following ASCs transplantation. And ASCs transplantation attenuated MCT-induced PAH albeit less than the antagomir treated group. Finally, we found that miR-191 repressed the expression of bone morphogenetic protein receptor 2 (BMPR2) in HPAECs and PAH rats. Thus, we conjectured that miR-191, in ASCs and ASCs-Exos, plays an important role in PAH via regulation of BMPR2. These findings are expected to contribute to promising therapeutic strategies for treating PAH in the future.
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Pilegaard, Henriette, Gerasimos Terzis, Andrew Halestrap, and Carsten Juel. "Distribution of the lactate/H+ transporter isoforms MCT1 and MCT4 in human skeletal muscle." American Journal of Physiology-Endocrinology and Metabolism 276, no. 5 (May 1, 1999): E843—E848. http://dx.doi.org/10.1152/ajpendo.1999.276.5.e843.
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The profiles of the lactate/H+ transporter isoforms [monocarboxylate transporter isoforms (MCT)] MCT1 and MCT4 (formerly MCT3 of Price, N. T., V. N. Jackson, and A. P. Halestrap. Biochem. J. 329: 321–328, 1998) were studied in the soleus, triceps brachii, and vastus lateralis muscles of six male subjects. The fiber-type compositions of the muscles were evaluated from the occurrence of the myosin heavy chain isoforms, and the fibers were classified as type I, IIA, or IIX. The total content of MCT1 and MCT4 was determined in muscle homogenates by Western blotting, and MCT1 and MCT4 were visualized on cross-sectional muscle sections by immunofluorescence microscopy. The Western blotting revealed a positive, linear relationship between the MCT1 content and the occurrence of type I fibers in the muscle, but no significant relation was found between MCT4 content and fiber type. Moreover, the interindividual variation in MCT4 content was much larger than the interindividual variation in MCT1 content in homogenate samples. The immunofluorescence microscopy showed that within a given muscle section, the MCT4 isoform was clearly more abundant in type II fibers than in type I fibers, whereas only minor differences existed in the occurrence of the MCT1 isoform between type I and II fibers. Together the present results indicate that the content of MCT1 in a muscle varies between different muscles, whereas fiber-type differences in MCT1 content are minor within a given muscle section. In contrast, the content of MCT4 is clearly fiber-type specific but apparently quite similar in various muscles.
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Hussien, Rajaa, and George A. Brooks. "Mitochondrial and plasma membrane lactate transporter and lactate dehydrogenase isoform expression in breast cancer cell lines." Physiological Genomics 43, no. 5 (March 2011): 255–64. http://dx.doi.org/10.1152/physiolgenomics.00177.2010.
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We hypothesized that dysregulation of lactate/pyruvate (monocarboxylate) transporters (MCT) and lactate dehydrogenase (LDH) isoforms contribute to the Warburg effect in cancer. Therefore, we assayed for the expression levels and the localizations of MCT ( 1 , 2 , and 4 ), and LDH (A and B) isoforms in breast cancer cell lines MCF-7 and MDA-MB-231 and compared results with those from a control, untransformed primary breast cell line, HMEC 184. Remarkably, MCT1 is not expressed in MDA-MB-231, but MCT1 is expressed in MCF-7 cells, where its abundance is less than in control HMEC 184 cells. When present in HMEC 184 and MCF-7 cells, MCT1 is localized to the plasma membrane. MCT2 and MCT4 were expressed in all the cell lines studied. MCT4 expression was higher in MDA-MB-231 compared with MCF-7 and HMEC 184 cells, whereas MCT2 abundance was higher in MCF-7 compared with MDA-MB-231 and HMEC 184 cells. Unlike MCT1, MCT2 and MCT4 were localized in mitochondria in addition to the plasma membrane. LDHA and LDHB were expressed in all the cell-lines, but abundances were higher in the two cancer cell lines than in the control cells. MCF-7 cells expressed mainly LDHB, while MDA-MB-231 and control cells expressed mainly LDHA. LDH isoforms were localized in mitochondria in addition to the cytosol. These localization patterns were the same in cancerous and control cell lines. In conclusion, MCT and LDH isoforms have distinct expression patterns in two breast cancer cell lines. These differences may contribute to divergent lactate dynamics and oxidative capacities in these cells, and offer possibilities for targeting cancer cells.
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Zhao, Guoliang, Yuxun Zhou, Zhanbo Xu, Yadong Zhou, and Jiang Wu. "Hierarchical Multi-Supervision Multi-Interaction Graph Attention Network for Multi-Camera Pedestrian Trajectory Prediction." Proceedings of the AAAI Conference on Artificial Intelligence 36, no. 4 (June 28, 2022): 4698–706. http://dx.doi.org/10.1609/aaai.v36i4.20395.
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Pedestrian trajectory prediction has become an essential underpinning in various human-centric applications including but not limited to autonomous vehicles, intelligent surveillance system and social robotics. Previous research endeavors mainly focus on single camera trajectory prediction (SCTP), while the problem of multi-camera trajectory prediction (MCTP) is often overly simplified into predicting presence in the next camera. This paper addresses MCTP from a more realistic yet challenging perspective, by redefining the task as a joint estimation of both future destination and possible trajectory. As such, two major efforts are devoted to facilitating related research and advancing modeling techniques. Firstly, we establish a comprehensive multi-camera Scenes Pedestrian Trajectory Dataset (mcScenes), which is collected from a real-world multi-camera space combined with thorough human interaction annotations and carefully designed evaluation metrics. Secondly, we propose a novel joint prediction framework, namely HM3GAT, for the MCTP task by building a tailored network architecture. The core idea behind HM3GAT is a fusion of topological and trajectory information that are mutually beneficial to the prediction of each task, achieved by deeply customized networks. The proposed framework is comprehensively evaluated on the mcScenes dataset with multiple ablation experiments. Status-of-the-art SCTP models are adopted as baselines to further validate the advantages of our method in terms of both information fusion and technical improvement. The mcScenes dataset, the HM3GAT, and alternative models are made publicly available for interested readers.
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Kaur, Manpreet, Mayank, Deepak Bains, Gagandeep Singh, Navneet Kaur, and Narinder Singh. "The solvent-free one-pot multicomponent tandem polymerization of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) catalyzed by ionic-liquid@Fe3O4 NPs: the development of polyamide gels." Polymer Chemistry 12, no. 8 (2021): 1165–75. http://dx.doi.org/10.1039/d0py01769h.
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Solvent-free MCTP via Biginelli DHPMs catalyzed by a non-toxic magnetic catalyst (IL1–2@ Fe3O4) in a one-pot reaction was illustrated for the development of fluorescent non-conjugated polyamide gels.
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Téllez-Arreola, José Luis, Malan Silva, and Ataúlfo Martínez-Torres. "MCTP-1 modulates neurotransmitter release in C. elegans." Molecular and Cellular Neuroscience 107 (September 2020): 103528. http://dx.doi.org/10.1016/j.mcn.2020.103528.
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Hérubel, François, Saïd El Mouatassim, Pierre Guérin, René Frydman, and Yves Ménézo. "Genetic expression of monocarboxylate transporters during human and murine oocyte maturation and early embryonic development." Zygote 10, no. 2 (May 2002): 175–81. http://dx.doi.org/10.1017/s096719940200223x.
Full textAbstract:
During the early preimplantation stages of human embryos, pyruvate and lactate, but not glucose, are the preferred energy substrates. Transport of these monocarboxylates is mediated, in mammalian cells, by a family of transporters, designated as monocarboxylate transporters (MCTs). Human and mouse genetic expression of MCT members 1, 2, 3, 4 and basigin, a chaperone protein of MCT1 and MCT4, was qualitatively analysed using the reverse transcription nested polymerase chain reaction (RT-nested PCR) in immature oocytes (germinal vesicle stage; GV), in non-fertilised metaphase II (MII) oocytes and in embryos from 2-cell stage to blastocysts. Transcripts encoding for MCT1 and MCT2 were present, under a polyadenylated form, in the majority of the human and mouse oocytes and early embryos. MCT3 transcripts were not detected in either human or mouse. MCT4 mRNA was not detected in human oocytes and embryos, but was present in mouse oocytes and embryos. This fact could imply differences in lactate transport and regulation of intracellular pH between human and murine early embryos. Basigin transcripts were present in mouse and human MII oocytes and preimplantation embryos, but were not detected at GV stage. However, using 3' end-specific primers in the RT reaction instead of Oligo(dT)12-18 primers, transcripts encoding for this protein were then detected at GV stage in both species. This result suggests that a regulated polyadenylation process occurs during oocyte maturation for these transcripts. Thus, basigin mRNA can be considered as a marker of oocyte cytoplasmic maturation in human and mouse species.
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Shah, Mehul, Kirit Patel, and Pravin B. Sehgal. "Monocrotaline pyrrole-induced endothelial cell megalocytosis involves a Golgi blockade mechanism." American Journal of Physiology-Cell Physiology 288, no. 4 (April 2005): C850—C862. http://dx.doi.org/10.1152/ajpcell.00327.2004.
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Pyrrolizidine alkaloids initiate disease in the lung (pulmonary hypertension), liver (veno-occlusive disease and cirrhosis), and kidneys (afferent arteriolar block and mesangiolysis) by inducing a megalocytotic phenotype in target endothelial and parenchymal cells. A “hit-and-run” type of exposure to the bioactive pyrrolizidine results, within 2–3 days, in enlarged cells with large nuclei and enlarged Golgi and endoplasmic reticulum, while the cells remain in G2/M block. In the present study, we recapitulated monocrotaline pyrrole (MCTP)-induced megalocytosis in cultures of bovine pulmonary arterial endothelial cells (PAEC), human Hep3B hepatocytes, human type II-like alveolar epithelial cells (A549), and human pulmonary arterial smooth muscle cells (PASMC) and investigated the subcellular mechanism involved. There was an inverse relationship between reduction in caveolin (Cav)-1 levels and stimulation of promitogenic STAT3 and ERK1/2 cell signaling. In megalocytotic PAEC, the Golgi scaffolding protein GM130 was shifted from membranes with heavy density to those with a lighter density. This lighter Golgi fraction was enriched for hypo-oligomeric Cav-1, indicating dysfunctional trafficking of cargo. Immunofluorescence imaging studies confirmed the trapping of Cav-1 in a GM130-positive Golgi compartment. There was an increase in Ser25 phosphorylation of GM130 (typically a prelude to Golgi fragmentation and mitosis) and increased association between pGM130, cdc2 kinase, and Cav-1. Nevertheless, megalocytotic MCTP-treated cells showed reduced entry into mitosis upon stimulation with 2-methoxyestradiol (2-ME), reduced 2-ME-induced Golgi fragmentation, and a slowing of Golgi reassembly after nocodazole-induced fragmentation. These data suggest that a disruption of the trafficking and mitosis sensor functions of the Golgi may represent the subcellular mechanism leading to MCTP-induced megalocytosis (“the Golgi blockade hypothesis”).
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Ramljak, Sanja, Matthias Schmitz, Cendrine Repond, Inga Zerr, and Luc Pellerin. "Altered mRNA and Protein Expression of Monocarboxylate Transporter MCT1 in the Cerebral Cortex and Cerebellum of Prion Protein Knockout Mice." International Journal of Molecular Sciences 22, no. 4 (February 4, 2021): 1566. http://dx.doi.org/10.3390/ijms22041566.
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The effect of a cellular prion protein (PrPc) deficiency on neuroenergetics was primarily analyzed via surveying the expression of genes specifically involved in lactate/pyruvate metabolism, such as monocarboxylate transporters (MCT1, MCT2, MCT4). The aim of the present study was to elucidate a potential involvement of PrPc in the regulation of energy metabolism in different brain regions. By using quantitative real-time polymerase chain reaction (qRT-PCR), we observed a marked reduction in MCT1 mRNA expression in the cortex of symptomatic Zürich I Prnp−/− mice, as compared to their wild-type (WT) counterparts. MCT1 downregulation in the cortex was accompanied with significantly decreased expression of the MCT1 functional interplayer, the Na+/K+ ATPase α2 subunit. Conversely, the MCT1 mRNA level was significantly raised in the cerebellum of Prnp−/− vs. WT control group, without a substantial change in the Na+/K+ ATPase α2 subunit expression. To validate the observed mRNA findings, we confirmed the observed change in MCT1 mRNA expression level in the cortex at the protein level. MCT4, highly expressed in tissues that rely on glycolysis as an energy source, exhibited a significant reduction in the hippocampus of Prnp−/− vs. WT mice. The present study demonstrates that a lack of PrPc leads to altered MCT1 and MCT4 mRNA/protein expression in different brain regions of Prnp−/− vs. WT mice. Our findings provide evidence that PrPc might affect the monocarboxylate intercellular transport, which needs to be confirmed in further studies.
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Joshi, Amit S., Joey V. Ragusa, William A. Prinz, and Sarah Cohen. "Multiple C2 domain–containing transmembrane proteins promote lipid droplet biogenesis and growth at specialized endoplasmic reticulum subdomains." Molecular Biology of the Cell 32, no. 12 (June 1, 2021): 1147–57. http://dx.doi.org/10.1091/mbc.e20-09-0590.
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MCTPs can tubulate the ER via reticulon homology domains. They localize to ER subdomains that are sites of lipid droplet (LD) biogenesis. MCTP reticulon homology domains promote LD biogenesis, while C2 domains mediate ER-LD contacts to promote LD growth. MCTPs may function more broadly to link ER tubules with organelle contact sites.
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Reynaert, N., M. Coghe, B. Heijmen, J. Jansen, S. Van der Marck, D. Schaart, M. Tomsej, C. Van vliet-Vroegindeweij, C. De Wagter, and W. Van der Zee. "77 Reporting of the NCS working group on MCTP." Radiotherapy and Oncology 76 (September 2005): S45—S46. http://dx.doi.org/10.1016/s0167-8140(05)81055-2.
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Liu, Lu, Chunying Li, Zhi Wei Norman Teo, Bin Zhang, and Hao Yu. "The MCTP-SNARE Complex Regulates Florigen Transport in Arabidopsis." Plant Cell 31, no. 10 (August 22, 2019): 2475–90. http://dx.doi.org/10.1105/tpc.18.00960.
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Ovens, Matthew J., Andrew J. Davies, Marieangela C. Wilson, Clare M. Murray, and Andrew P. Halestrap. "AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7–10." Biochemical Journal 425, no. 3 (January 15, 2010): 523–30. http://dx.doi.org/10.1042/bj20091515.
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In the present study we characterize the properties of the potent MCT1 (monocarboxylate transporter 1) inhibitor AR-C155858. Inhibitor titrations of L-lactate transport by MCT1 in rat erythrocytes were used to determine the Ki value and number of AR-C155858-binding sites (Et) on MCT1 and the turnover number of the transporter (kcat). Derived values were 2.3±1.4 nM, 1.29±0.09 nmol per ml of packed cells and 12.2±1.1 s−1 respectively. When expressed in Xenopus laevis oocytes, MCT1 and MCT2 were potently inhibited by AR-C155858, whereas MCT4 was not. Inhibition of MCT1 was shown to be time-dependent, and the compound was also active when microinjected, suggesting that AR-C155858 probably enters the cell before binding to an intracellular site on MCT1. Measurement of the inhibitor sensitivity of several chimaeric transporters combining different domains of MCT1 and MCT4 revealed that the binding site for AR-C155858 is contained within the C-terminal half of MCT1, and involves TM (transmembrane) domains 7–10. This is consistent with previous data identifying Phe360 (in TM10) and Asp302 plus Arg306 (TM8) as key residues in substrate binding and translocation by MCT1. Measurement of the Km values of the chimaeras for L-lactate and pyruvate demonstrate that both the C- and N-terminal halves of the molecule influence transport kinetics consistent with our proposed molecular model of MCT1 and its translocation mechanism that requires Lys38 in TM1 in addition to Asp302 and Arg306 in TM8 [Wilson, Meredith, Bunnun, Sessions and Halestrap (2009) J. Biol. Chem. 284, 20011–20021].
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Bonen, Arend, Dragana Miskovic, Mio Tonouchi, Kathleen Lemieux, Marieangela C. Wilson, André Marette, and Andrew P. Halestrap. "Abundance and subcellular distribution of MCT1 and MCT4 in heart and fast-twitch skeletal muscles." American Journal of Physiology-Endocrinology and Metabolism 278, no. 6 (June 1, 2000): E1067—E1077. http://dx.doi.org/10.1152/ajpendo.2000.278.6.e1067.
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The expression of two monocarboxylate transporters (MCTs) was examined in muscle and heart. MCT1 and MCT4 proteins are coexpressed in rat skeletal muscles, but only MCT1 is expressed in rat hearts. Among six rat fast-twitch muscles (red and white gastrocnemius, plantaris, extensor digitorum longus, red and white tibialis anterior) there was an inverse relationship between MCT1 and MCT4 ( r = −0.94). MCT1 protein was correlated with MCT1 mRNA ( r = 0.94). There was no relationship between MCT4 mRNA and MCT4 protein. MCT1 ( r = −0.97) and MCT4 ( r = 0.88) protein contents were correlated with percent fast-twitch glycolytic fiber. When normalized for their mRNAs, MCT1 but not MCT4 was still correlated with the percent fast-twitch glycolytic fiber composition of rat muscles ( r = −0.98). MCT1 and MCT4 were also measured in plasma membranes (PM), triads (TR), T tubules (TT), sarcoplasmic reticulum (SR), and intracellular membranes (IM). There was an intracellular pool of MCT4 but not of MCT1. The MCT1 subcellular distribution was as follows: PM (100%) > TR (31.6%) > SR (15%) = TT (14%) > IM (1.7%). The MCT4 subcellular distribution was considerably different [PM (100%) > TR (66.5%) > TT (36%) = SR (43%) > IM (24%)]. These studies have shown that 1) the mechanisms regulating the expression of MCT1 (transcriptional and posttranscriptional) and MCT4 (posttranscriptional) are different and 2) differences in MCT1 and MCT4 expression among muscles, as well as in their subcellular locations, suggest that they may have different roles in muscle.
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Dong, Yu Zhen, Seung Hyuk Kwon, Hyoung Jin Choi, Pillaiyar Puthiaraj, and Wha-Seung Ahn. "Electroresponsive Polymer–Inorganic Semiconducting Composite (MCTP–Fe3O4) Particles and Their Electrorheology." ACS Omega 3, no. 12 (December 13, 2018): 17246–53. http://dx.doi.org/10.1021/acsomega.8b02731.
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Kore, Anilkumar, Melissa Hodeib, and Zhongting Hu. "Chemical Synthesis of LNA-mCTP and Its Application for MicroRNA Detection." Nucleosides, Nucleotides and Nucleic Acids 27, no. 1 (January 2008): 1–17. http://dx.doi.org/10.1080/15257770701571693.
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Gill, Ravinder K., Seema Saksena, Waddah A. Alrefai, Zaheer Sarwar, Jay L. Goldstein, Robert E. Carroll, Krishnamurthy Ramaswamy, and Pradeep K. Dudeja. "Expression and membrane localization of MCT isoforms along the length of the human intestine." American Journal of Physiology-Cell Physiology 289, no. 4 (October 2005): C846—C852. http://dx.doi.org/10.1152/ajpcell.00112.2005.
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Recent studies from our laboratory and others have demonstrated the involvement of monocarboxylate transporter (MCT)1 in the luminal uptake of short-chain fatty acids (SCFAs) in the human intestine. Functional studies from our laboratory previously demonstrated kinetically distinct SCFA transporters on the apical and basolateral membranes of human colonocytes. Although apical SCFA uptake is mediated by the MCT1 isoform, the molecular identity of the basolateral membrane SCFA transporter(s) and whether this transporter is encoded by another MCT isoform is not known. The present studies were designed to assess the expression and membrane localization of different MCT isoforms in human small intestine and colon. Immunoblotting was performed with the purified apical and basolateral membranes from human intestinal mucosa obtained from organ donor intestine. Immunohistochemistry studies were done on paraffin-embedded sections of human colonic biopsy samples. Immunoblotting studies detected a protein band of ∼39 kDa for MCT1, predominantly in the apical membranes. The relative abundance of MCT1 mRNA and protein increased along the length of the human intestine. MCT4 (54 kDa) and MCT5 (54 kDa) isoforms showed basolateral localization and were highly expressed in the distal colon. Immunohistochemical studies confirmed that human MCT1 antibody labeling was confined to the apical membranes, whereas MCT5 antibody staining was restricted to the basolateral membranes of the colonocytes. We speculate that distinct MCT isoforms may be involved in SCFA transport across the apical or basolateral membranes in polarized colonic epithelial cells.
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Mulyana, Asep, Utari Sumarmo, and Rudi Kurniawan. "The Role of Problem Solving Approach on Student’s Mathematical Critical Thinking Ability and Disposition." (JIML) JOURNAL OF INNOVATIVE MATHEMATICS LEARNING 1, no. 3 (September 30, 2018): 256. http://dx.doi.org/10.22460/jiml.v1i3.p256-267.
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This study was a pre test-post test experimental control group design having a goal to analyze the role of prior mathematics ability (PMA) and Problem Solving Approach (PSA) on student’s mathematical critical thinking ability (MCTA) and disposition (MCTD). The study involved 65 eleventh grade students, a prior mathematics ability (PMA), a MCTA test, a MCTD scale. The study found that PMA and PSA took roles on obtaining student’s MCTA and MCTD, those were the higher student’s PMA the study found the higher students MCTA and MCTD. Beside that, on MCTA and its N Gain, entirely and with low and medium PMA students getting treatment with PSA attained better grades than the grades of students taught by conventional teaching (CT); and for entirely and with medium and high PMA, student recieving treatment with PSA obtained higher grades on MCTA and MCTD than student taught by CT and those grades were at good grade level. The other findings, there was no association between MCTA and MCTD, and no interaction between PAM and teaching approaches toward MCTA and on MCTD and student learn actively during PSA
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Ha, B., C. L. Lucas, G. W. Henry, E. G. Frantz, J. I. Ferreiro, and B. R. Wilcox. "Effects of chronically elevated pulmonary arterial pressure and flow on right ventricular afterload." American Journal of Physiology-Heart and Circulatory Physiology 267, no. 1 (July 1, 1994): H155—H165. http://dx.doi.org/10.1152/ajpheart.1994.267.1.h155.
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The effects of pulsatile hemodynamics on right ventricle-pulmonary circulation interactions were studied in control lambs and in two lamb models of altered pulmonary hemodynamics induced at infancy: elevated pulmonary arterial pressure (PAP) was created by the infusion of monocrotaline pyrrole (MCTP), and elevated pulmonary arterial blood flow was obtained by the creation of an arteriovenous fistula (Shunt). High-fidelity PAP, midvessel Doppler blood velocity (PAV), and cardiac output (CO) were measured in open-chest, anesthetized lambs. PAV waveforms were normalized to match the measured CO. Measured pressure and flow signals were separated in the time domain into forward and backward components. Pulmonary input impedance and indexes quantifying the timing of the reflected wave pulse (beginning of reflected pulse, duration of reflected pulse in systole, and duration of reflected wave in diastole) were calculated for each group. Results indicate that in control animals the reflected wave returned late in systole and extended through much of diastole, thereby increasing diastolic pressure like a counterpulsation balloon. No significant differences in the timing indexes were found between Shunt and control animals. In the MCTP group, the reflected wave returned significantly earlier than normal with the peak reflected pulse occurring before valve closure. The resulting augmentation of systolic pressure and, therefore, large pulse pressure is consistent with pressure waveforms observed in clinical pulmonary hypertension. We conclude that early wave reflection exerts a detrimental effect in pulmonary hypertension by unfavorably loading the still-ejecting right ventricle.
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Lai, Y. L., J. W. Olson, and M. N. Gillespie. "Ventilatory dysfunction precedes pulmonary vascular changes in monocrotaline-treated rats." Journal of Applied Physiology 70, no. 2 (February 1, 1991): 561–66. http://dx.doi.org/10.1152/jappl.1991.70.2.561.
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Rats with established monocrotaline (MCT)-induced pulmonary hypertension also exhibit a profound increase in lung resistance (RL) and a decrease in lung compliance. Because airway/lung dysfunction could precede and influence the evolution of MCT-induced pulmonary vascular disease, it is important to establish the temporal relationship between development of pulmonary hypertension and altered ventilatory function in MCT-treated rats. To resolve this issue, we segregated 47 young Sprague-Dawley rats into four groups: control (n = 13), MCT1 (n = 9), MCT2 (n = 11), and MCT3 (n = 14). Each MCT rat received a single subcutaneous injection of MCT (60 mg/kg) 1 MCT1), 2 (MCT2), or 3 (MCT3) wk before the functional study. At 1 wk after MCT, significant increases in RL and alveolar wall thickness were observed, as was a significant decrease in carbon monoxide diffusing capacity (DLCO). Medial thickness of pulmonary arteries (50-100 microns OD) and right ventricular hypertrophy were not observed until 2 and 3 wk post-MCT, respectively. Coincident with the right ventricular hypertrophy at 3 wk post-MCT were decreased DLCO and increased alveolar wall thickness and lung dry weight. Pressure-volume curves of air-filled and saline-filled lungs showed marked rightward shifts during the 1st and 2nd wk after MCT administration and then decreased at the 3rd wk. These data suggest that MCT-induced alterations in airway/lung function preceded those of pulmonary vasculature and, therefore, implicate airway/lung dysfunctions as potentially contributing to the later development of pulmonary vascular abnormalities.
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Sepponen, K., N. Koho, E. Puolanne, M. Ruusunen, and A. R. Pösö. "Distribution of monocarboxylate transporter isoforms MCT1, MCT2 and MCT4 in porcine muscles." Acta Physiologica Scandinavica 177, no. 1 (December 19, 2002): 79–86. http://dx.doi.org/10.1046/j.1365-201x.2003.01051.x.
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Hashimoto, Takeshi, Shinya Masuda, Sadayoshi Taguchi, and George A. Brooks. "Immunohistochemical analysis of MCT1, MCT2 and MCT4 expression in rat plantaris muscle." Journal of Physiology 567, no. 1 (August 2005): 121–29. http://dx.doi.org/10.1113/jphysiol.2005.087411.
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Numsomran, Arjin, Thanit Trisuwannawat, and Vittaya Tipsuwanporn. "Adaptive Fractional Order PIλDμ Control for Multi-Configuration Tank Process (MCTP) Toolbox." International Journal of Intelligent Engineering and Systems 11, no. 5 (October 31, 2018): 21–35. http://dx.doi.org/10.22266/ijies2018.1031.03.
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