S100a6 Interacts With Melusin And Attenuates Stress-Induced Cardiomyocyte Apoptosis

Introduction: Cardiac overexpression of S100A6, a member of the family of EF-hand calcium binding proteins attenuates left ventricular remodeling and preserves cardiac function after myocardial infarction. The exact mechanism behind this protective effect is unclear. Hypothesis: Recent in vitro evidence suggests S100A6 binding to melusin a muscle specific chaperone protein associated with the β1 integrin cytoplasmic domain.Whether the S100A6-melusin interaction is physiologically relevant and an element of a cardioprotective pathway is unknown. Methods: We induced myocardial infarction (MI) via left anterior descending coronary artery ligation in rats. Results: At 28 days post MI, S100A6 and melusin mRNA and protein increased 2-3.5 fold over basal, predominantly in the peri-infarct zone. We found by immunoprecipitation and immunofluorescence that S100A6 binds to melusin in the peri-infarct zone and that the interaction requires the presence of calcium. In vitro, exposure of cultured rat neonatal cardiomyo...