title: Taurine attenuates methamphetamine-induced autophagy and apoptosis in PC12 cells through mTOR signaling pathway.
abstract: Methamphetamine (METH), a commonly abused psychostimulant, has been shown to induce neuronal damage by causing reactive oxygen species (ROS) formation, apoptosis and autophagy. Taurine (2-aminoethanesulfonic acid) is involved in several physiological actions in the brain, including neuroprotection, osmoregulation and neurotransmission. In this study, we investigate the protective effect of taurine against METH-induced neurotoxicity in PC12 cells and the underlying mechanism. The results showed that taurine significantly increased the cell viability inhibited by METH. LC3-II expression was elevated by METH treatment, whereas such increase was obviously attenuated by taurine. Co-treatment of taurine strongly reversed the decline of antioxidase activities induced by METH. Moreover, phosphorylated mammalian target of rapamycin (p-mTOR) was significantly inhibited by METH, whereas complementation of taurine markedly increased the expression of p-mTOR in PC12 cells, rather than phosphorylated Erk. Interestingly, taurine-induced decreasing expression of LC3-II was partially blocked by pretreatment of RAD001, an mTOR inhibitor. These results indicated that taurine inhibits METH-induced autophagic process through activating mTOR rather than Erk signaling. Collectively, our study shows that taurine protects METH-induced PC12 cells damage by attenuating ROS production, apoptosis and autophagy, at least in part, via mTOR signaling pathway.
authors.affiliation: National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Hu
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Bu
authors.forename: Wenjie
authors.initials: W
authors.lastname: Lu
authors.forename: Yi
authors.initials: Y
authors.lastname: Deng
authors.forename: Ruiming
authors.initials: R
authors.lastname: Zhu
authors.forename: Xue
authors.initials: X
authors.lastname: Shao
authors.forename: Jing
authors.initials: J
authors.lastname: Hou
authors.forename: Jinxuan
authors.initials: J
authors.lastname: Zhao
authors.forename: Hongyu
authors.initials: H
authors.lastname: Li
authors.forename: Baolai
authors.initials: B
authors.lastname: Zhang
authors.forename: Yina
authors.initials: Y
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
authors.forename: Yinglan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Cen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D005434:Flow Cytometry; D005979:Glutathione Peroxidase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D013654:Taurine / Q000494:pharmacology*
chemical_list: D000697:Central Nervous System Stimulants; D018696:Neuroprotective Agents; D013654:Taurine; D008694:Methamphetamine; D002374:Catalase; D005979:Glutathione Peroxidase; D058570:TOR Serine-Threonine Kinases