RESUMO
Methyl protodioscin (MPD) is reported to relieve angina pectoris and myocardial ischemia, and mitochondrial E3 ubiquitin ligase 1 (Mul1) plays a key role in maintaining mitochondrial functions. Bioinformatic analysis shows potential interactions between MPD and Mul1. This study aims to explore whether MPD could protect rat brain against ischemia/reperfusion (I/R) injury through regulation of Mul1/ superoxide dismutase 2 (SOD2) pathway. The SD rat brains were subjected to 2â¯h of ischemia following by 24â¯h of reperfusion, which showed I/R injury (increase in neurological deficit score and infarct volume), up-regulation of Mul1 and down regulation of SOD2, these phenomena were attenuated by MPD treatment (3 or 10â¯mg/kg, i.g.). Consistently, in cultured HT22 cells, hypoxia-reoxygenation (H/R) treatment induced cellular injury (apoptosis and LDH release) concomitant with up-regulation of Mul1 and down regulation of SOD2, these phenomena were blocked in the presence of MPD (5⯵M). Knockdown of Mul1 could also decrease SOD2 protein levels in HT22 cells accompanied by alleviation of H/R injury (reduction of apoptosis and LDH release). In agreement with the change of SOD2, reactive oxygen species generation was increased in H/R-treated HT22 cells while decreased in the presence of MPD. Based on these observations, we conclude that upregulation of Mul1 in rat brain contributes to cerebral I/R injury via suppression of SOD2 and that MPD protects rat brain from I/R injury through a mechanism involving regulation of Mul1/SOD2 pathway.
