PIASA, a novel peptide, prevents SH-SY5Y neuroblastoma cells against rotenone-induced toxicity.

This investigation explored the neuroprotective effect of PIASA a newly designed peptide – VCSVY in in-silico and in opposition to rotenone stimulated oxidative stress, mitochondrial dysfunction, and apoptosis in an SH-SY5Y cellular model.
Docking and visualization of the PIASA and rotenone was progressed against mitochondrial respiratory complex I (MCI). The in-silico analysis showed that PIASA had interaction to the binding sites of rotenone which may reduce the rotenone interaction and its toxicity too. The SH-SY5Y cells were segregated into four experimental groups: Group I: untreated control cells; Group II: rotenone-only (100 nM) treated cells; Group III: PIASA (5 µM) + rotenone (100 nM) treated cells; and Group IV: PIASA-only (5 μM) treated cells.
We evaluated the cell viability, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), apoptosis (dual staining technique), nuclear morphological changes (Hoechst staining technique), expression of BAX, Bcl-2, cyt c, pro-caspase 3, and caspases 3, -6, -8, -9 and cleaved caspases 3 by western blot analysis. In SH-SY5Y cells, we further observed the cytotoxicity, oxidative stress and mitochondrial dysfunction in rotenone-only treated cells, whereas pretreatment of PIASA attenuated the rotenone mediated toxicity. Moreover, rotenone toxicity is caused by complex I inhibition, which leads to mitochondrial dysfunction, increased BAX while down regulating the Bcl2 expression and cyt c release and then finally caspases activation. PIASA pretreatment prevented the cytotoxic effects via the normalization of apoptotic marker expressions influenced by rotenone. In addition, pre-clinical studies are acceptable in rodents to make use of PIASA as a revitalizing remedial agent especially for PD in future.
Collectively, our results proposed that PIASA mitigated rotenone stimulated oxidative stress, mitochondrial dysfunction, and apoptosis in rotenone induced SH-SY5Y cells.

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