G6PD plays a neuroprotective role in brain ischemia through promoting pentose phosphate pathway.

G6PD plays a neuroprotective role in brain ischemia through promoting pentose phosphate pathway.
Free Radic Biol Med. 2017 Aug 17;:
Authors: Cao L, Zhang D, Chen J, Qin YY, Sheng R, Feng X, Chen Z, Ding Y, Li M, Qin ZH
Abstract
TIGAR-regulated pentose phosphate pathway (PPP) plays a critical role in the neuronal survival during cerebral ischemia/reperfusion. Glucose-6-phosphate dehydrogenase (G6PD) is a rate-limiting enzyme in PPP and thus, we hypothesized that it plays an essential role in anti-oxidative defense through producing NADPH. The present study investigated the regulation and the role of G6PD in ischemia/reperfusion-induced neuronal injury with in vivo and in vitro models of ischemic stroke. The results showed that the levels of G6PD mRNA and protein were increased after ischemia/reperfusion. In vivo, lentivirus-mediated G6PD overexpression in mice markedly reduced neuronal damage after ischemia/reperfusion insult, while lentivirus-mediated G6PD knockdown exacerbated it. In vitro, overexpression of G6PD in cultured primary neurons decreased neuronal injury under oxygen and glucose deprivation/reoxygenation (OGD/R) condition, whereas knockdown of G6PD aggravated it. Overexpression of G6PD increased levels of NADPH and reduced form of glutathione (rGSH), and ameliorated ROS-induced macromolecular damage. On the contrary, knockdown of G6PD executed the opposite effects in mice and in primary neurons. Supplementation of exogen...

Source: Free Radical Biology and Medicine - August 17, 2017 Category: Biology Authors: Cao L, Zhang D, Chen J, Qin YY, Sheng R, Feng X, Chen Z, Ding Y, Li M, Qin ZH Tags: Free Radic Biol Med Source Type: research