GABA attenuates ETEC-induced intestinal epithelial cell apoptosis involving GABAAR signaling and the AMPK-autophagy pathway

GABA 减弱 ETEC 诱导的肠上皮细胞凋亡,涉及 GABAAR 信号传导和 AMPK 自噬通路

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作者:Yaoyao Xia, Siyuan Chen, Yuanyuan Zhao, Shuai Chen, Ruilin Huang, Guoqiang Zhu, Yulong Yin, Wenkai Ren, Jinping Deng

Abstract

Enterotoxigenic Escherichia coli (ETEC) triggers diarrhea in humans and livestock. We have previously showed that ETEC promotes intestinal epithelial cell apoptosis and increases gamma-aminobutyric acid (GABA) concentration in the jejunum, suggesting that GABA might mediate ETEC-induced apoptosis. Here, we found that GABA alleviates ETEC-induced intestinal barrier dysfunctions, including ETEC-induced apoptosis both in vivo and in vitro. Interestingly, the alleviation of GABA on ETEC-induced apoptosis largely depends on autophagy. Mechanistically, GABA attenuates ETEC-induced apoptosis via activating GABAAR signaling and the AMPK-autophagy pathway. These findings highlight that maintaining intestinal GABA concentration could alleviate intestinal ETEC infection.

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