Alpha-lipoic acid upregulates SIRT1-dependent PGC-1α expression and protects mouse brain against focal ischemia.
Từ khóa
trừu tượng
OBJECTIVE
Silent mating type information regulation 2 homolog 1 (SIRT1) is a class III histone deacetylase and activates peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) which attenuates oxidative damage. Alpha-lipoic acid (ALA) has been proven to protect the rat brain against cerebral ischemia injury by reducing oxidative stress. However, the underlying mechanisms are poorly understood. In this study, we investigated the potential neuroprotection and the possible role of ALA in SIRT1 pathway.
METHODS
Male CD-1 mice were randomly assigned to three groups: Sham, permanent middle cerebral artery occlusion (pMCAO) and ALA group (ALA, 50mg/kg). ALA was administered intraperitoneally 30min prior to ischemia in the ALA group. Neurological deficit, infarct volume, and brain edema were detected at 24h after cerebral ischemia. Immunohistochemistry, western blot and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression of SIRT1 and PGC-1α. Activities of superoxide dismutase (SOD) were measured by assay kits.
RESULTS
Compared with the pMCAO group, the ALA group significantly ameliorated neurological deficit, lessened infarct volume and brain edema, increased the expression of SIRT1, PGC-1α and activities of SOD (P<0.05).
CONCLUSIONS
ALA protected the mouse brain against ischemic damage, and this protection may be through up-regulating SIRT1-dependent PGC-1α expression.
