Role Of 3-Mercaptopyruvate Sulfur Transferase In Cardiac Ischemia/Reperfusion Injury

Introduction: Hydrogen sulfide (H 2 S) is endogenously produced by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfur transferase (3MST). CSE contributes significantly to cardiac H 2 S and exerts protective roles in ischemia/reperfusion (I/R) injury and heart failure. Recently, 3MST has attracted significant attention as a source of H 2 S; however, its function in the heart remains unknown. Hypothesis: 3MST localizes in the cytosol and mitochondria, a key organelle for energy production and cardiomyocyte survival. We, thus, investigated the role of 3MST in the setting of myocardial I/R injury. Methods and Results: 3MST transcripts were 2.5-fold higher compared to CSE in the murine heart. 3MST was localized mainly in cardiomyocytes and smooth muscle cells. More than 60% of 3MST expressed in cardiomyocytes was co-localized with mito-tracker. Despite complete absence of 3MST protein, free H 2 S and sulfane sulfur levels were not different between 3MST KO and wild-type (WT) mice. 3MST KO exhibited no differences in heart rate, fractional shortening, ejection fraction, intraventricular septum length, left ventricular (LV) end-diastolic diameter, end-systolic diameter and posterior wall thickness. CBS, CSE, endothelial nitric oxide synthase and soluble guanylate cyclase were expressed to similar levels in 3MST KO and WT, while cGMP-dependent protein kinase was elevated in 3MST mice. Male, but not female, 3MST KO mice subjected to 30 min ischemia (LAD ligation) followed by 2 hrs of reperfusion exhibited reduced myocardial infarct size (29± 3% vs. 43 ± 3 %, p 2 O 2 compared to the GFP-infected cells. Conclusions: We conclude that 3MST, unlike CSE, negatively impacts cardiomyocyte survival following ischemia/reperfusion. Thus, 3MST inhibition may represent a novel target for cardioprotection.