谷氨酰胺通过抑制JNK活化保护猪颗粒细胞免受氧化应激诱导凋亡

Abstract

Oxidative stress-induced granulosa cells (GCs) apoptosis is believed to be the hallmark of follicular atresia. Although a large number of studies have shown that some molecules in follicular fluid (FF) are important to granulosa cell survival, the key substances in FF associated with the regulation of granulosa cell apoptosis have not been fully elucidated. Herein, metabolomics analysis showed that the glutamine level in healthy FF was significantly higher than that in atretic FF. Then, an oxidative stress model was built up by adding hydrogen peroxide (H 2 O 2 ). The results revealed that treating porcine GCs with H 2 O 2 significantly elevated the reactive oxygen species (ROS) levels ( p < 0.01) and caused a marked decrease in cell viability ( p < 0.0001). Exogenous glutamine alleviated the intracellular ROS accumulation and porcine GCs apoptosis induced by H 2 O 2 ( p < 0.05). Knocking down glutamine synthetase (GLUL), the key gene for glutamine synthesis, diminished cell viability ( p < 0.01) and increased intracellular ROS levels and porcine GCs apoptosis ( p < 0.05). Both H 2 O 2 and the knockdown of GLUL activated the JNK signalling pathway, while glutamine decreased the activation of JNK to protect porcine GCs from oxidative stress-induced apoptosis. These findings indicate that glutamine protects porcine GCs from oxidative stress-induced apoptosis by inhibiting JNK activation, which is of great significance for clarifying the molecular mechanisms behind follicular atresia.