文献类型：期刊文献

英文题名：Bisphenol A induces apoptosis and autophagy in murine osteocytes MLO-Y4: Involvement of ROS-mediated mTOR/ULK1 pathway

作者：Zhang, Yun[1];Yan, Ming[2];Kuang, Shumeng[1];Lou, Yiqiang[1];Wu, Shouqian[1];Li, Yurong[1];Wang, Zihan[1];Mao, Hongjiao[1]

机构：[1]Shaoxing Univ, Coll Med, Huancheng West Rd 508, Shaoxing 312000, Peoples R China;[2]HangZhou Dianzi Univ, Sch Automat, 1158 2nd Ave, Hangzhou 310018, Peoples R China

年份：2022

卷号：230

外文期刊名：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

收录：SCI-EXPANDED(收录号：WOS:000740090700002)、、Scopus(收录号：2-s2.0-85121579411)、WOS

基金：This work was supported by Natural Science Foundation of Zhejiang Province (LY21H060001) and National Natural Science Foundation of China (81700936) .

语种：英文

外文关键词：BPA; Osteocytes; Apoptosis; Autophagy; mTOR; ULK1 pathway; ROS

外文摘要：Bisphenol A (BPA) is a widely environmental endocrine disruptor. The accumulated BPA in humans is toxic to osteoblasts and osteoclasts, but few studies focused on the effects of BPA on osteocytes, the most abundant bone cell type, contributing to the development and metabolism of bone. Here, we reported that BPA (50, 100, 200 mu mol/L) inhibited the cell viability of osteocytes MLO-Y4, promoted G0/G1 phase arrest and apoptosis in a dose-dependent manner. BPA treatment significantly increased the levels of autophagy-regulated proteins including Beclin-1 and LC3-II along with the decrease of p62, accompanied by the elevation of autophagy flux and the accumulation of acidic vacuoles, which was blocked by the autophagy inhibitor bafilomycin A1 (BafA1). Furthermore, BPA significantly inhibited the mammalian target of rapamycin (mTOR) and activated Unc-51 like autophagy activating kinase 1 (ULK1) signaling, leading to the decreased p-mTOR/mTOR ratio and the increased p-ULK1/ULK1 ratio. The mTOR activator MHY1485 (MHY) or the ULK1 inhibitor SBI-0206965 (SBI) prevented autophagy and enhanced apoptosis caused by BPA, respectively. In addition, BPA increased the levels of intra-cellular reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased antioxidant enzymes nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) levels, resulting in oxidative stress. The ROS scavenger N-acetylcysteine (NAC) attenuated BPA-induced the mTOR/ULK1 pathway activation, apoptosis and autophagy. Collectively, ROS-mediated mTOR/ULK1 signaling is involved in BPA-induced apoptosis and auto-phagy in osteocytes MLO-Y4. Our data first provide in vitro evidence that apoptosis and autophagy as cellular mechanisms for the toxic effect of BPA on osteocytes, thereby advancing our understanding of the potential role of osteocytes in the adverse effect of BPA on bone health.