Advanced oxidation protein products attenuate the autophagy-lysosome pathway in ovarian granulosa cells by modulating the ROS-dependent mTOR-TFEB pathway

• DOI: 10.1038/s41419-024-06540-w
• Publication Date: 2024-02-21T13:02:18Z
• Authors: Xing-Yu Zhou; Yun-Hui Lai; Jun Zhang; Ying Li; Xiao-Min Wu; Yi-Zhen Yang; Xiao-Fei Zhang; Lin-Zi Ma; Ke-Ming Zheng; Yu-Dong Liu; Zhe Wang; Shi-Ling Chen
• Keywords: TFEB

Abstract Oxidative stress dysfunction has recently been found to be involved in the pathogenesis of premature ovarian insufficiency (POI). Previously, we that advanced oxidation protein products (AOPPs) plasma were elevated women with POI and had an adverse effect on granulosa cell proliferation. However, mechanism underlying effects AOPPs autophagy-lysosome pathway regulation cells remains unclear. In this study, autophagy lysosomal biogenesis mechanisms explored by a series vitro experiments KGN COV434 lines. AOPP-treated rat models employed determine negative systems vivo. We increased AOPP levels activated mammalian target rapamycin (mTOR) pathway, inhibited autophagic response cells. Furthermore, scavenging reactive oxygen species (ROS) N-acetylcysteine blockade mTOR or via starvation alleviated AOPP-induced inhibitory biogenesis, suggesting these are ROS-mTOR dependent. The expression nuclear translocation transcription factor EB (TFEB), key regulator function, also impaired AOPP-activated pathway. addition, TFEB overexpression attenuated impairment flux Chronic stimulation vivo ovaries. results highlight lead ROS-mTOR-TFEB signaling participate POI.