Sestrin2 emerges as a regulator of ROS-mediated oxidative stress and apoptosis in the cadmium-induced liver injury of rare minnow (Gobiocypris rarus).

Cadmium plays no know functional role in any life-form, but has severe effects. To elucidate the mechanism of cadmium-induced liver injury, 120 rare minnows were used to collect samples or culture liver cell. Animal assays results showed that exposed to 5 µg/L or 10 µg/L cadmium for 28 d caused histological changes with increased histopathological condition index (Ih), significantly increased the cadmium content and increased levels of reactive oxygen species (ROS) of rare minnow liver. The changed Sestrin2 (Sesn2) and nuclear factor erythroid 2-related factor 2 (Nrf2) expressions were clarified that Sesn2 was closely related with Nrf2 pathway. Western blot supported the event of apoptosis in cadmium exposed liver tissues as compared to control, which was further confirmed by downregulated expression of pro-apoptotic genes and upregulated pro-apoptosis gene bcl2 expression. Cell assays further validated that cadmium exposure decreased liver cell viability, markedly increased ROS production and pro-apoptotic genes expression and suppressed antioxidant genes expression after Sesn2 knockout. Altogether, the present results demonstrated that Sesn2 can facilitated Nrf2 pathway via ROS-mediated oxidative stress and apoptosis after cadmium exposure. These data indicated that Sesn2 might be a new target to study the mechanism of cadmium-induced liver injury.