The involvement of calcium in the toxic effect of 4‐methylethcathinone on SH‐SY5Y cells

Abstract

AbstractNeurotoxicity 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.