Effect of cornel iridoid glycoside on PP2Ac phosphorylation in okadaic acid-induced neurotoxicity cells
10.16438/j.0513-4870.2018-0188
- VernacularTitle:山茱萸环烯醚萜苷对冈田酸拟阿尔茨海默病细胞模型PP2A催化亚基C磷酸化及其调节酶Src的影响
- Author:
Cui-cui YANG
1
;
Xue-xian KUAI
1
;
Li ZHANG
1
;
Ya-li LI
1
;
Lin LI
1
;
Lan ZHANG
1
Author Information
1. Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing Engineering Research Center for Nerve System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China
- Publication Type:SPECIAL REPORTS
- Keywords:
cornel iridoid glycoside;
tau protein;
protein phosphatase 2A;
Src;
Alzheimer's disease
- From:
Acta Pharmaceutica Sinica
2018;53(7):1036-1041
- CountryChina
- Language:Chinese
-
Abstract:
Alzheimer's disease (AD) is the most common neurodegenerative disease in the aging population. Abnormal hyperphosphorylation of tau is the main cause of AD. Protein phosphatases 2A (PP2A) can increase the hyperphosphorylation of tau. Cornel iridoid glycoside (CIG) is one of the main components extracted from Cornus of ficinalis. The aim of the present study was to investigate the effects and the underlying mechanisms of CIG on enhancing PP2A activity. SK-N-SH cells were exposed to 20 nmol·L-1 okadaic acid (OA, an inhibitor of PP2A) for 6 h to induce the hyper-phosphorylation of tau, in order to define the effect of CIG on the activity of PP2A and posttranslational modification of PP2A catalytic subunit C (PP2Ac). We found that OA significantly decreased PP2A activity, increased the phosphorylation of PP2Ac, and enhanced tau hyper-phosphorylation. Pre-incubation of CIG significantly attenuated the OA-induced tau hyper-phosphorylation at Ser 199/202 and Ser 396, and recovered the activity of PP2A. CIG inhibited PP2Ac phosphorylation at Tyr 307 and increased Src phosphorylation. In conclusion, the mechanism of CIG inhibition of tau hyper-phosphorylation was activation of PP2A to reduce the level of p-Src for a reduction of PP2Ac phosphorylation at Tyr307.
