Isorhamnetin activates Sirt1/PGC-1α signaling pathway to inhibit MPP+-induced SH-SY5Y cell injury
10.16438/j.0513-4870.2019-0205
- VernacularTitle:异鼠李素激活Sirt1/PGC-1α信号通路抑制MPP+诱导的SH-SY5Y细胞损伤
- Author:
Wen ZHANG
1
;
Jun-ke SONG
1
;
Xiao-yu ZHU
2
;
Hai-guang YANG
1
;
Qi-meng ZHOU
1
;
Qi-tai XU
2
;
Guan-hua DU
1
Author Information
1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
2. Hainan Green Areca Technology Development Co. LTD., Ding'an 571200, China
- Publication Type:Research Article
- Keywords:
isorhamnetin;
silent mating type information regulation 2 homolog 1;
peroxisome proliferator-activated receptor γ coactivator-1α;
neuroprotection
- From:
Acta Pharmaceutica Sinica
2019;54(11):1976-1981
- CountryChina
- Language:Chinese
-
Abstract:
We studied the protective effect and mechanism of isorhamnetin (ISO) on 1-methyl-4-phenylpyridiniumion (MPP+)-induced SH-SY5Y cells injury. MPP+-induced SH-SY5Y cell injury model was established, and cell viability was measured by MTT and LDH methods. The activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in cells were determined to investigate the level of oxidative stress. DCFH-DA and MitoSOX fluorescence probes were used to detect the levels of intracellular reactive oxygen species (ROS) and mitochondria superoxide, respectively. JC-1 fluorescence probe was used to detect the changes of mitochondrial membrane potential. Western blot and immunofluorescence methods were used to determine the expressions of Sirt1 and PGC-1 proteins, as well as the expression levels of apoptosis-related proteins Bax and Bcl-2. MPP+ at the dose of 500 μmol·L-1 significantly reduced SH-SY5Y cells viability to 52.46% and increased LDH release to 417.63%. ISO at 5 and 15 μmol·L-1 significantly increased the expression of Sirt1 and PGC-1α, inhibited LDH release, reduced intracellular ROS and mitochondria superoxide, inhibited the decline of mitochondrial membrane potential and increased cell viability to 61.61% and 67.55%. In addition, ISO could downregulate the expression of Bax and upregulate the expression of Bcl-2 to reduce cell apoptosis. ISO-mediated inhibition of apoptosis could be reversed by Sirt1 specific inhibitor Sirtinol. Through activating Sirt1/PGC-1α signaling pathway, ISO could reduce oxidative stress injury and inhibit cell apoptosis to protect cells from MPP+ injury.
