Abstract
Background New interventions are required to prevent the loss of cardiomyocytes associated with myocardial ischemia and with the reperfusion injury that follows revascularisation. Recent studies have shown that compounds releasing hydrogen sulfide (H2S) can have cardioprotective effects [1] . However, these compounds are generally effective only at high (μM) concentrations and release is not well controlled, increasing the potential for cytotoxicity. H2S is produced endogenously and targeting the pathways that regulate availability in heart may be a more promising therapeutic approach. The present study aimed to characterise the distribution of the H2S synthesising enzymes, cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE) and mercaptopyruvate sulfurtransferase (MPST), and of H2S degrading enzyme, thiosulfate sulfurtransferase (TST) in the murine heart and in liver, an important site of H2S metabolism. Methods RNA and protein were prepared from heart and liver collected from 10 week old male C57BL/6J mice for quantitative RT-PCR and Western blotting. Further tissue was formalin fixed, processed and wax embedded before sectioning for immunohistochemistry. Results qRT-PCR showed high relative gene expression for all H2S metabolising enzymes in the liver. Cardiac tissue displayed high relative gene expression of TST & CSE, moderate expression of CBS and low expression of MPST. Western blots confirmed the presence of protein for TST & all H2S synthesising enzymes within heart & liver homogenates. Immunohistochemical staining of fixed tissue sections located CSE to vascular smooth muscle in the heart, while CBS & MPST were found in the vascular endothelium. Cardiomyocytes were immunoreactive for all enzymes. In hepatocytes, immunoreactive TST, CBS & MPST are found in hepatocytes throughout the liver, while CSE immunoreactivity is notably intensified around the central vein, responsible for hepatic venous return. Conclusion The murine myocardium and liver have the capacity to regulate local H2S availability via three separate synthetic pathways at least one degradative pathway which have distinctive cellular localisations. Future studies will investigate whether metabolic & synthetic enzyme expression and H2S availability is differentially regulated following ischaemia and reperfusion.
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