Antioxidant effects of celastrol against hydrogen peroxide-induced oxidative stress in the cell model of amyotrophic lateral sclerosis.
- Author:
Ying-Hui LI
1
;
Shao-Bo LIU
1
;
Hao-Yun ZHANG
2
;
Feng-Hua ZHOU
3
;
Yong-Xin LIU
3
;
Qiang LU
3
;
Ling YANG
4
Author Information
1. College of Biology Science and Technology, Weifang Medical University, Weifang 261053, China.
2. College of Clinic Medicine, Weifang Medical University, Weifang 261053, China. haoyunzh@wfmc.edu.cn.
3. College of Clinic Medicine, Weifang Medical University, Weifang 261053, China.
4. College of Pharmacy, Weifang Medical University, Weifang 261053, China.
- Publication Type:Journal Article
- From:
Acta Physiologica Sinica
2017;69(6):751-758
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the anti-oxidative effect of celastrol on HO-induced oxidative stress in the cell model of amyotrophic lateral sclerosis (ALS) and its molecular mechanism, NSC34 motor neuron-like cells were transfected with EGFP-G93A-SOD1 plasmid and used as in vitro ALS cell model. SOD1transfected NSC34 cells were treated with different doses of HOand celastrol. The survival rate of the cells was detected by CCK-8 assay, and malondialdehyde (MDA) content was detected by corresponding kit. The mRNA expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione S-transferases (GST) were detected by real-time PCR. The activation of intracellular MEK/ERK and PI3K/Akt signal pathways was detected by Western blot. The results showed that pre-incubation of celastrol (50 nmol/L) for 4 h prior to HO(10 μmol/L) co-treatment for another 24 h significantly attenuated HO-induced cell death and MDA level in SOD1transfected NSC34 cells. Real-time PCR showed that the mRNA expressions of GCLC and GST were enhanced with pre-incubation of celastrol. Celastrol quickly induced phosphorylation of ERK1/2 and Akt within 30 min and 1 h respectively in SOD1transfected NSC34 cells. Pharmacological inhibitors of MEK (PD98059, 10 μmol/L) or Akt (MK2206, 10 μmol/L) could reverse the phosphorylation of ERK1/2 and Akt, and abolish up-regulation of GCLC and GST induced by celastrol at mRNA levels. Taken together, we conclude that celastrol exerts a beneficial antioxidant effect in SOD1NSC34 cells, which might be dependent on MEK/ERK and PI3K/Akt signaling pathway activation.
