Cardioprotective SUR2A promotes stem cell properties of cardiomyocytes

摘要

Development of stem cell therapies to treat cardiovascular disease is limited by the ability to regulate stem cell differentiation and by poor cell survival once grafted to sites of damage in the heart [1]. SUR2A belongs to a group of "atypical" ABC proteins as, although possessing a structure of an ABC protein, it does not seem to mediate transport. Instead, SUR2A binds to inward rectifier Kir6.2 to form cardiac sarcolemmal ATP-sensitive K+ channels. The binding of SUR2A to Kir6.2 serves a dual purpose: 1) it allows translocation of the channel to the sarcolemma and 2) contributes to the channel regulation (reviewed in ref. [2]). In vivo, K~Atp channels exist as a multiprotein complex that, besides pore-forming Kir6.1/Kir6.2 and regulatory SUR2A subunits, also contain a string of glycolytic and ATP-producing enzymes including creatine kinase, GAPDH and M-LDH. It has been shown that the changes in levels of SLJR2A alone have a profound effect on myocardial susceptibility to different types of metabolic stresses including hypoxia, ischemia, ischemia-reperfusion and stimulation with beta-adrenergic agonists (reviewed in ref.).