Sestrin2 aggravates oxidative stress of neurons by decreasing the expression of Nrf2

OBJECTIVE: Oxidative injury is an essential part of the pathological changes of cerebral ischemia-reperfusion. Sestrin2 (Sesn2), a conserved antioxidant protein, is activated under stress to protect cells against oxidative stress. This study mainly explored the function and mechanism of Sesn2 during cerebral ischemia-reperfusion injury in rats.

MATERIALS AND METHODS: Oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary neurons was established. MTS and LDH (lactate dehydrogenase) kit were used to detect cell viability and cell damage by colorimetric method. The superoxide dismutase (SOD) kit and malondialdehyde (MDA) kit were used to access the level of SOD and MDA in neurons. To establish a model of middle cerebral artery occlusion (MCAO) in adult male Sprague-Dawley (SD) rats, the process of cerebral ischemia-reperfusion injury in animals was simulated. Western blot and immunofluorescence were utilized to further examine the relationship between the expression of Sesn2 and Nrf2 (nuclear factor E2 related factor 2).

RESULTS: Sesn2 aggravated neuronal damage and enhanced cell viability in OGD/R model. Intraventricular injection of Sesn2 siRNA lentivirus aggravated nerve function damage in MCAO model, increased cerebral infarction area and water content. Sesn2 overexpression resulted in the increase of total, nuclear levels of Nrf2, as well as the downstream proteins of Nrf2, sulfiredoxin1 (Srx1) and thioredoxin1 (Trx1). On the contrary, after knockdown of Sesn2, we obtained the opposite result. Knockdown of Sesn2 reduced Nrf2, Srx1 and Trx1 levels in rat cerebral cortex in MCAO model.

CONCLUSIONS: Sesn2 promoted the transfer of nuclear Nrf2 to the cytoplasm, it decreased the expressions of Nrf2 and its downstream proteins, Srx1 and Trx1. Meanwhile, it increased the cerebral ischemia-reperfusion injury by changing the distribution of Nrf2.

L'articolo Sestrin2 aggravates oxidative stress of neurons by decreasing the expression of Nrf2 sembra essere il primo su European Review.

https://ift.tt/2MmuWI9