Journal article
K. Moshal, Munish Kumar, N. Tyagi, P. Mishra, Naira S. Metreveli, W. Rodríguez, S. Tyagi
American Journal of Physiology. Heart and Circulatory Physiology, 2009
American Journal of Physiology. Heart and Circulatory Physiology, 2009
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APA
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Moshal, K., Kumar, M., Tyagi, N., Mishra, P., Metreveli, N. S., Rodríguez, W., & Tyagi, S. (2009). Restoration of contractility in hyperhomocysteinemia by cardiac-specific deletion of NMDA-R1. American Journal of Physiology. Heart and Circulatory Physiology.
Chicago/Turabian
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Moshal, K., Munish Kumar, N. Tyagi, P. Mishra, Naira S. Metreveli, W. Rodríguez, and S. Tyagi. “Restoration of Contractility in Hyperhomocysteinemia by Cardiac-Specific Deletion of NMDA-R1.” American Journal of Physiology. Heart and Circulatory Physiology (2009).
MLA
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Moshal, K., et al. “Restoration of Contractility in Hyperhomocysteinemia by Cardiac-Specific Deletion of NMDA-R1.” American Journal of Physiology. Heart and Circulatory Physiology, 2009.
BibTeX Click to copy
@article{k2009a,
title = {Restoration of contractility in hyperhomocysteinemia by cardiac-specific deletion of NMDA-R1.},
year = {2009},
journal = {American Journal of Physiology. Heart and Circulatory Physiology},
author = {Moshal, K. and Kumar, Munish and Tyagi, N. and Mishra, P. and Metreveli, Naira S. and Rodríguez, W. and Tyagi, S.}
}
Abstract
Homocysteine (HCY) activated mitochondrial matrix metalloproteinase-9 and led to cardiomyocyte dysfunction, in part, by inducing mitochondrial permeability (MPT). Treatment with MK-801 [N-methyl-d-aspartate (NMDA) receptor antagonist] ameliorated the HCY-induced decrease in myocyte contractility. However, the role of cardiomyocyte NMDA-receptor 1 (R1) activation in hyperhomocysteinemia (HHCY) leading to myocyte dysfunction was not well understood. We tested the hypothesis that the cardiac-specific deletion of NMDA-R1 mitigated the HCY-induced decrease in myocyte contraction, in part, by decreasing nitric oxide (NO). Cardiomyocyte-specific knockout of NMDA-R1 was generated using cre/lox technology. NMDA-R1 expression was detected by Western blot and confocal microscopy. MPT was determined using a spectrophotometer. Myocyte contractility and calcium transients were studied using the IonOptix video-edge detection system and fura 2-AM loading. We observed that HHCY induced NO production by agonizing NMDA-R1. HHCY induced the MPT by agonizing NMDA-R1. HHCY caused a decrease in myocyte contractile performance, maximal rate of contraction and relaxation, and prolonged the time to 90% peak shortening and 90% relaxation by agonizing NMDA-R1. HHCY decreased contraction amplitude with the increase in calcium concentration. The recovery of calcium transient was prolonged in HHCY mouse myocyte by agonizing NMDA-R1. It was suggested that HHCY increased mitochondrial NO levels and induced MPT, leading to the decline in myocyte mechanical function by agonizing NMDA-R1.
