Ischemia-Selective Cardioprotection by Malonate for Ischemia/Reperfusion Injury.

ABSTRACT:

Background

Inhibiting SDH (succinate dehydrogenase), with the competitive inhibitor malonate, has shown promise in ameliorating ischemia/reperfusion injury. However, key for translation to the clinic is understanding the mechanism of malonate entry into cells to enable inhibition of SDH, its mitochondrial target, as malonate itself poorly permeates cellular membranes. The possibility of malonate selectively entering the at-risk heart tissue on reperfusion, however, remains unexplored.

Methods

C57BL/6J mice, C2C12 and H9c2 myoblasts, and HeLa cells were used to elucidate the mechanism of selective malonate uptake into the ischemic heart upon reperfusion. Cells were treated with malonate while varying pH or together with transport inhibitors. Mouse hearts were either perfused

SUBMITTER: Prag HA 

PROVIDER: S-EPMC9426742 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature