PIASA, A Novel Peptide, Prevents SH-SY5Y Neuroblastoma Cells against Rotenone-induced Toxicity.
Parkinson’s disease
SH-SY5Y cells
apoptosis
cell viability
degeneration
peptide
Journal
Current molecular pharmacology
ISSN: 1874-4702
Titre abrégé: Curr Mol Pharmacol
Pays: United Arab Emirates
ID NLM: 101467997
Informations de publication
Date de publication:
2023
2023
Historique:
received:
14
08
2021
revised:
03
12
2021
accepted:
06
12
2021
pubmed:
2
5
2022
medline:
17
3
2023
entrez:
1
5
2022
Statut:
ppublish
Résumé
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. 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. 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. Collectively, our results propose that PIASA mitigated rotenone-stimulated oxidative stress, mitochondrial dysfunction, and apoptosis in rotenone-induced SH-SY5Y cells.
Sections du résumé
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.
Identifiants
pubmed: 35490311
pii: CMP-EPUB-122945
doi: 10.2174/1874467215666220427103045
doi:
Substances chimiques
Rotenone
03L9OT429T
Caspase 3
EC 3.4.22.-
bcl-2-Associated X Protein
0
Proto-Oncogene Proteins c-bcl-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
393-410Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.