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2000
Volume 16, Issue 3
  • ISSN: 1874-4672
  • E-ISSN:

Abstract

Background and Objective: This investigation explores 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. Methods: Docking and visualization of the PIASA and rotenone were progressed against mitochondrial respiratory complex I (MCI). The in-silico analysis showed PIASA to have interaction with 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. Results: We evaluated the cell viability, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), apoptosis (dual staining technique), nuclear morphological changes (Hoechst staining technique), the expressions of BAX, Bcl-2, cyt c, pro-caspase 3, and caspase 3, -6, -8, -9, and cleaved caspase 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 expression, while downregulating the Bcl-2 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 the future. Conclusion: Collectively, our results propose that PIASA mitigated rotenone-stimulated oxidative stress, mitochondrial dysfunction, and apoptosis in rotenone-induced SH-SY5Y cells.

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/content/journals/cmp/10.2174/1874467215666220427103045
2023-06-01
2024-11-08
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  • Article Type:
    Research Article
Keyword(s): apoptosis; cell viability; degeneration; Parkinson’s disease; peptide; SH-SY5Y cells
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