Over-expression of survivin could prevent the oxidative stress and toxicity of rotenone in SH-SY۵Y cells

Objective(s): It is important to find novel therapeutic molecular targets for curing Parkinson’s disease (PD). Accordingly, this study aimed to evaluate the effect of over-expression of the survivin gene, a gene frequently reported as neuroprotective, on the in vitro model of PD. Materials and Methods: Survivin was over-expressed in SH-SY۵Y cells. Next, the cells were treated with rotenone (۵۰۰ nM) for ۲۴ hr. Then, viability and the total antioxidant capacity were assessed. The expression levels of ۱۵ important genes of key cellular processes (oxidative stress, apoptosis, cell cycle, and autophagy) were assessed. The studied genes included survivin, superoxide dismutase, catalase, BAX, bcl۲, caspase ۳, caspase ۸, caspase ۹, p۵۳, SMAC, β-catenin, mTOR, AMPK, ATG۷, RPS۱۸. The apoptosis level and the frequency of cell cycle stages were assessed by flow cytometry. For analyzing the data, the ANOVA test followed by Tukey’s test was used to evaluate the significant differences between the experimental groups. P<۰.۰۵ was considered significant. Results: Survivin could significantly decrease the rotenone-induced apoptosis in SH-SY۵Y cells. The rotenone treatment led to down-regulation of catalase and up-regulation of bax, bcl۲, caspase ۳, caspase ۸, P۵۳, β-catenin, and ATG۷. Survivin could significantly neutralize the effect of rotenone in most the genes. It could also increase the total antioxidant capacity of SH-SY۵Y cells. Conclusion: Survivin could prevent the toxic effect of rotenone on SH-SY۵Y cells during the development of in vitro PD model via regulating the genes of key cellular processes, including anti-oxidation, apoptosis, cell cycle, and autophagy. 

Keywords:

Apoptosis , Autophagy , Oxidative stress , Parkinson’s disease , Survivin