P13 A hypothesis on the mechanism of CSE protection of myocardial cells during hypoxia

Abstract

Cystathionine gamma-lyase (CSE) is the predominant enzyme responsible for the production of endogenous hydrogen sulfide (H 2 S) in cardiovascular system, and hypoxia is one of the pathogenetic conditions frequently encountered by the cardiovascular system. We would like to answer the question whether hypoxia affects CSE expression on levels of promoter, message RNA and protein. In the present study, we studied the effect of hypoxia on CSE expression in the mammalian cells during hypoxia. Our results showed that hypoxia regulated CSE expression in the mammalian cells in a complex manner, and CSE transcription went through a repression and recovery period while total mRNA and protein levels increased during hypoxia. Based on the above analysis, we proposed a hypothesis about the mechanism of CSE protection on the myocardial cells. This hypothesis explained the mechanism as follows. Under the hypoxic condition which induced some cardiomyocyte apoptosis, the peroxisomes of cardiomyocyte released hydrogen peroxide (H 2 O 2 ) out into the vascular endothelial cells of small arteries in the heart. The proper concentration of H 2 O 2 promoted the recovery increase of CSE expression in the vascular endothelial cells via the nuclear factor kappa-B signal pathway. The up-regulation of CSE expression in the vascular endothelial cells produced more hydrogen sulfide H 2 S, which accelerated vascular smooth muscular cells (SMCs) vasodilation. Therefore, the improvement of blood circulation increased the quantity of oxygen supply to the heart, decreased the infarct size, and attenuated cardiomyocyte apoptosis. Taken together, we believe that the CSE gene in the mammalian cells is a prominent protective component in response to hypoxia through transcriptional and post transcriptional mRNA regulation. Meanwhile, we speculate that the up-regulation of CSE expression provides one of the effective protections on the mammalian cells under hypoxic conditions.