Premium
PINK1 overexpression protects against cerebral ischemia through Parkin regulation
Author(s) -
Wen Youliang,
Gu Yueming,
Tang Xiaodong,
Hu Ziwei
Publication year - 2020
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22855
Subject(s) - pink1 , parkin , oxidative stress , mitochondrion , reactive oxygen species , downregulation and upregulation , apoptosis , microbiology and biotechnology , programmed cell death , biology , chemistry , pharmacology , medicine , endocrinology , biochemistry , disease , parkinson's disease , gene
Mitochondrial dynamics and function are important for cell survival regulation under stress. In this study, we report that cerebral ischemia/reperfusion (I/R) injury significantly reduced mitochondrial function through reduced PTEN‐induced kinase 1 (PINK1) expression, ATP (Adenosine triphosphate) levels, and increased oxidative stress compared to sham rats. PINK1 overexpression mice significantly improved mitochondrial function by increased mitochondrial complex I, II, and III activities and ATP levels with concomitant decline in reactive oxygen species levels. PINK1 overexpression mice after I/R injury significantly reduced apoptosis through downregulation of cytochrome c, p53 expressions compared to cerebral I/R injury rats. Furthermore, we showed from parkin siRNA studies that PINK1 regulated phosphorylation parkin is critical to the protection against cerebral I/R injury. Altogether, we show that PINK1 mediated parkin regulation is key to the protection against cerebral I/R injury through regulation of mitochondrial function and apoptosis.