Metformin restores the mitochondrial membrane potentials in association with a reduction in TIMM23 and NDUFS3 in MPP+-induced neurotoxicity in SH-SY5Y cells
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Date
2019-09-10
Journal Title
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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
Description
Table of contents
Keywords
MPP +, Metformin, Mitochondria, SH - SY5Y cells, Parkinson ’ s disease