Alpha-lipoic acid alleviates the 6-OHDA-induced SH-SY5Y cell damage by inhibiting autophagy via AMPK/mTOR pathway / 中华老年医学杂志

ABSTRACT

Objective To investigate the effects of α-lipoic acid(ALA)on 6-hydroxydopamine(6-OHDA)-induced autophagy in human neuroblastoma(SH-SYSY)cells and its possible mechanisms.Methods SH-SYSY cells were divided into 5 groupsblank control group (group A),ALA group (group B),6-OHDA group(group C),ALA+6-OHDA group(group D),and rapamycin(RAPA)group (group E).The cell viability,cell apoptosis,and oxidative stress were assayed and analyzed in A-D group.The expression of autophagy-related proteins LC3-Ⅱ,AMP-activated protein kinase(AMP-K),phosphorylated AMPK (p-AMPK),the mammalian target of rapamycin (mTOR) and p-mTOR were detected by Western blot in A-E group.Results Compared with the blank control group,the 6-OHDA group significantly reduced the cell viability(P ＜ 0.01) and p-mTOR protein expression (P ＜0.05),and increased the cellular apoptosis rate(P＜0.01),oxidative stress level(P ＜0.01),LC3-Ⅱ protein expression(P＜0.05,with the highest level at 6 h after treatment),and p-AMPK protein expression(P＜＜0.05).There was no significant difference in these indices between ALA group and the blank control group.Compared with 6-OHDA group,ALA+ 6-OHDA group showed that the cell viability(P ＜ 0.01) and p-mTOR protein expression (P ＜ 0.05) were increased,while the cellular apoptosis rate(P＜0.01),oxidative stress level(P＜0.01),LC3-Ⅱ protein expression(P ＜0.05),and p-AMPK protein expression (P ＜ 0.05)were decreased.Conclusions The 6-OHDA can induce oxidative stress and autophagy in SH-SY5Y cells and decrease the cell viability.ALA can alleviate the 6-OHDA-induced cell injury possibly by inhibiting autophagy via AMPK/mTOR pathway.