文献类型：期刊文献

英文题名：The involvement of calcium in the toxic effect of 4-methylethcathinone on SH-SY5Y cells

作者：Zhang, Wei[1];Cao, Fangqi[1,2];Li, Ming[1];Xu, Zhiwen[1];Sun, Jing[3];Huang, Zhiwei[4];Shi, Ping[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Shanghai Res Inst Criminal Sci & Technol, Shanghai Key Lab Crime Scene Evidence, Shanghai, Peoples R China;[3]Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Key Lab Qinghai Tibet Plateau Biol Resourc, Xining, Peoples R China;[4]Donghua Univ, Coll Biol Sci & Med Engn, Shanghai, Peoples R China

年份：2024

卷号：44

期号：4

起止页码：553

外文期刊名：JOURNAL OF APPLIED TOXICOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001099762500001)】；

基金：The study was supported by grants from the National Natural Science Foundation of China (32171958), the Shanghai Municipal Natural Science Foundation (22ZR1400900), and the Development Project of Qinghai Provincial Key Laboratory (2022-ZJ-Y18).

语种：英文

外文关键词：4-methylethcathinone; autophagy; calcium ion; endoplasmic reticulum stress; G0/G1 cell cycle arrest

摘要：Neurotoxicity induced by psychoactive substances is often accompanied by an imbalance of intracellular calcium ions. It is unclear whether calcium ions play a role in the toxicity induced by psychoactive substances. In the present study, we aimed to evaluate the occurrence of calcium dysregulation and its contribution to cytotoxicity in human neurotypic SH-SY5Y cells challenged with a recently developed psychoactive substance 4-methylethcathinone (4-MEC). An increase in the intracellular calcium was detected by inductively coupled plasma atomic emission spectrometry and Fluo-3 AM dye in SH-SY5Y cells after being treated with 4-MEC. The increase of intracellular Ca2+ level mediated G0/G1 cell cycle arrest and ROS/endoplasmic reticulum stress-autophagy signaling pathways to achieve the toxicity of 4-MEC. In particular, N-acetyl-L-cysteine, a classical antioxidant, was found to be a potential treatment for 4-MEC-induced toxicity. Taken together, our results demonstrate that an increase in intracellular calcium content is one of the mechanisms of 4-MEC-induced toxicity. This study provides a molecular basis for the toxicity mechanism and therapeutic intervention of psychoactive substances. The present study aimed to evaluate calcium dysregulation occurrence and its contribution to cytotoxicity in human neurotypic SH-SY5Y cells challenged with a recently developed psychoactive substance 4-MEC. An increase in intracellular calcium was found in SH-SY5Y cells after being treated with 4-MEC. The increase of intracellular Ca2+ level mediated G0/G1 cell cycle arrest and ROS/endoplasmic reticulum stress-autophagy signaling pathways to achieve the toxicity of 4-MEC. N-acetyl-L-cysteine was found to be a potential treatment for 4-MEC-induced toxicity.