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چکیده
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Abstract: Parkinson's disease (PD) is a neurological disorder characterized by the loss of dopaminergic neurons in the substantia nigra as well as the accumulation of Levi bodies (LB) in these neurons. Mitochondria are known as semi-independent, dynamic organelles that are continuously dividing into healthy cells and recombining to form a dynamic network. These two processes of mitochondrial membrane fission and fusion are called mitochondrial dynamics. Mitochondrial fission is regulated by several proteins in the outer membrane. In mammals, the fis1 protein is one of the factors influencing mitochondrial fission. Mitochondrial dysfunction is recognized as a major factor in the progression of many diseases. Current research on PD is mostly done with SH-SY5Y neuroblastoma neuronal cell lines. Rotenone was used as an inhibitor of mitochondrial complex I to induce the Parkinson's disease model. Alpha-lipoic acid has antioxidant activity and has neuroprotective effects in various pathological conditions, including neuronal loss. Background: In the present study, following previous studies to further understand the role of mitochondrial dynamics in PD, it was determined to investigate the effective rotenone concentrations in SH-SY5Y neurons viability as well as the effect of alpha lipoic acid on cell survival in stress condition induce by rotenone. Genomic expression level of fis1 gene, in SH-SY5Y cell line treated with rotenone and alpha-lipoic acid was evaluated. Methods: The effect of rotenone toxicity on SH-SY5Y cell growth in presence of rotenone and alpha-lipoic acid was evaluated by MTT method. The expression of fis1 gene was then evaluated by real-time PCR. Results: Based on IC50 calculations, the toxicity of rotenone was determined at concentrations higher than 1 μM. Toxicity effect of two concentrations of 2.5- and 5- μM rotenone for 24 and 48 hours treatment showed a significant decrease in SH-SY5Y cells survival. Improved cell viability was observed in presence of 20 µM alpha-lipoic acid in SH-SY5Y cells treated by rotenone. The qPCR results of fis1 gene expression indicated a significant increase in SH-SY5Y cells treated with 5 µM rotenone (P <0.001). Conclusion: The results of this study show that the expression of a mitochondrial fission gene is altered in rotenone-treated SH-SY5Y cells in culture medium. Thus, mitochondrial dynamics may involve in the pathogenesis or control of Parkinson's disease.
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