Metformin restores the mitochondrial membrane potentials in association with a reduction in TIMM23 and NDUFS3 in MPP+-induced neurotoxicity in SH-SY5Y cells
Keywords:MPP, metformin, mitochondria, SH-SY5Y cells, Parkinson’s disease
SH-SY5Y cells exposed to l-methyl-4-phenylpyridinium (MPP+) develop mitochondrial dysfunction and other cellular responses similar to those that occur in the dopaminergic neurons of patients with Parkinson’s disease (PD). It has been shown in animal models of PD that neuronal death can be prevented by metformin, an anti-diabetic drug. Both MPP+ and metformin inhibit complex I of the mitochondrial respiratory chain. It has been reported that decreased levels of the mitochondrial inner membrane proteins TIMM23 and NDUFS3 are associated with the increased generation of reactive oxygen species and mitochondrial depolarization. In the present study, we investigated the effects of metformin on MPP+-induced neurotoxicity using differentiated human SH-SY5Y neuroblastoma cells. The results showed that pretreatment with metformin increased the viability of MPP+-treated SH-SY5Y cells. Pretreatment with metformin decreased the expression of TIMM23 and NDUFS3 in MPP+-treated SH-SY5Y cells. This was correlated with reduced mitochondrial fragmentation and an improvement in the mitochondrial membrane potential. These results suggest that metformin pretreatment protects against MPP+-induced neurotoxicity, and offer insights into the potential role of metformin in protecting against toxin-induced parkinsonism.
How to Cite
Authors who publish in this journal agree to the following terms:
- The authors keep the copyright and grant the journal the right of first publication under the terms of the Creative Commons Attribution license, CC BY 4.0. This licencse permits unrestricted use, distribution and reproduction in any medium, provided that the original work is properly cited.
- The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations.
- Because the advice and information in this journal are believed to be true and accurate at the time of publication, neither the authors, the editors, nor the publisher accept any legal responsibility for any errors or omissions presented in the publication. The publisher makes no guarantee, express or implied, with respect to the material contained herein.
- The authors can enter into additional contracts for the non-exclusive distribution of the journal's published version by citing the initial publication in this journal (e.g. publishing in an institutional repository or in a book).