Metformin restores the mitochondrial membrane potentials in association with a reduction in TIMM23 and NDUFS3 in MPP+-induced neurotoxicity in SH-SY5Y cells

Abstract

SH - SY5Y cells exposed to l - methyl - 4 - phenylpyridinium (MPP + ) develop mitochondrial dys- function and other cellular responses similar to th ose 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 resp iratory chain. It has been reported that decreased levels of the mitochondrial inner membrane proteins TI MM23 and NDUFS3 are associated with the in- creased generation of reactive oxygen species and mitochondrial de polarization. In the present study, we investigated the e ffects of metformin on MPP + - induced neurotoxicity using differen- tiated human SH - SY5Y neuroblastoma cells . The results showed that pretreatment with met- formin increased the viability of MPP + - treated SH - SY5Y cells. Pretreatment with metformin decreased the expr ession of TIMM23 and NDUFS3 in MPP + - treated SH - SY5Y cells. This was correlated with reduced mitochondrial fragmenta tion and an improvement in the mitochondrial membrane potential . These results suggest that metformin pretreatment protects against MPP + - induced neurotoxicity, and offer insights into th e potential role of me tformin in protecting against toxin - induced parkinsonism