P678 * S-glutathiolation of cMyBP-C reduces its phosphorylation and contributes to impairment of cardiac myocyte contractile function (original) (raw)

Cardiac myosin-binding protein C (cMyBP-C) plays a crucial role in regulating cardiac contraction and relaxation. In heart failure, cMyBP-C phosphorylation is reduced, contributing to impaired contractility. This study focuses on S-glutathiolation of cMyBP-C, mapping Cys249 as a key modification site. Experimental results show that S-glutathiolation diminishes cMyBP-C phosphorylation by PKA and CaMKIIa, leading to decelerated cross-bridge cycling kinetics in cardiac myocytes. Furthermore, an increase in S-glutathiolation correlates with reduced overall phosphorylation in heart failure patients, potentially contributing to contractile dysfunction.