文献类型：期刊文献

英文题名：Bisphenol A induces pyroptotic cell death via ROS/NLRP3/Caspase-1 pathway in osteocytes MLO-Y4

作者：Zhang, Yun[1];Yan, Ming[2];Shan, Weiyan[1];Zhang, Tao[1];Shen, Yunchen[1];Zhu, Ruirong[1];Fang, Jian[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, Baiyang St 2 Ave 1158, Hangzhou 310018, Peoples R China

年份：2022

卷号：159

外文期刊名：FOOD AND CHEMICAL TOXICOLOGY

收录：SCI-EXPANDED(收录号：WOS:000750833700007)、、Scopus(收录号：2-s2.0-85121443820)、WOS

基金：This work was supported by Natural Science Foundation of Zhejiang Province (LY21H060001) , National Natural Science Foundation of China (81700936) and Zhejiang Public Welfare Technology Application Research Project (LGF18H060006) .

语种：英文

外文关键词：BPA; Osteocytes; Pyroptosis; NLRP3; ROS

外文摘要：Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, is commonly used as a plasticizer to manufacture various food packaging materials. Evidence has demonstrated that BPA disturbed bone health. However, few studies focused on the effect of BPA on osteocytes, making up over 95% of all the bone cells. Here, we reported that BPA inhibited the cell viability of MLO-Y4 cells, and increased apoptosis in a dose-dependent manner. Furthermore, BPA up-regulated protein expressions of speck-like protein containing CARD (ASC), NLRP3, cleaved caspase-1 (Casp-1 p20) and cleaved gasdermin D (GSDMD-N), and increased the ratios of interleukin (IL)-113/pro-IL-113 and IL-18/pro-IL-18 in MLO-Y4 cells. BPA enhanced levels of lactate dehydrogenase (LDH), IL113 and IL-18 in culture supernatants. This pyroptotic death and the NLPR3 inflammasome activation were reversed by the caspase-1 inhibitor VX765 or the NLRP3 inflammasome inhibitor MCC950. Furthermore, BPA stimulated the production of intracellular reactive oxygen species (ROS), mitochondrial ROS (mtROS), elevated malondialdehyde (MDA) level and decreased superoxide dismutase (SOD) activity, which led to oxidative damage in MLO-Y4 cells. The ROS scavenger N-acetylcysteine (NAC) or the mitochondrial antioxidant MitoTEMPO inhibited the NLPR3 inflammasome activation and pyroptotic death induced by BPA. Collectively, our data suggest that BPA causes pyroptotic death of osteocytes via ROS/NLRP3/Caspase-1 pathway.