effect of dj-1 on the neuroprotection of astrocytes subjected to cerebral ischemia/reperfusion injury

Astrocytes are involved in neuroprotection, and dj-1 is an important antioxidant protein that is abundantly expressed in reactive astrocytes. however, the role of dj-1 in astrocytes’ neuroprotection in cerebral ischemia/reperfusion injury and its potential mechanism is unclear. thus, to explore effects and mechanisms of dj-1 on the neuroprotection of astrocytes, we used primary co-cultures of neurons and astrocytes under oxygen and glucose deprivation/reoxygenation in vitro and transient middle cerebral artery occlusion/reperfusion in vivo to mimic ischemic reperfusion insult. lentiviral was used to inhibit and upregulate dj-1 expression in astrocytes, and dj-1 sirna blocked dj-1 expression in rats. inhibiting dj-1 expression led to decreases in neuronal viability. dj-1 knockdown also attenuated total and nuclear nrf2 and glutathione (gsh) levels in vitro and vivo. similarly, loss of dj-1 decreased nrf2/are-binding activity and expression of nrf2/are pathway-driven genes. overexpression of dj-1 yielded opposite results. this suggests that the mechanism of action of dj-1 in astrocyte-mediated neuroprotection involve regulation of the nrf2/are pathway to increase gsh after cerebral ischemia/reperfusion injury. thus, dj-1 be a new therapeutic target for treating ischemia/reperfusion injury.