The role of melatonin in repairing of insulin signaling transduction defect induced by linoleic acid and its mechanism
10.13699/j.cnki.1001-6821.2015.20.019
- VernacularTitle:褪黑素对亚油酸导致的胰岛素信号转导缺陷的修复机制
- Author:
Xue-Dong WAN
1
;
Bo WANG
;
Qun-Li CHEN
;
San-Qiang LI
;
Shou-Min XI
Author Information
1. 河南科技大学 医学院 生物化学与分子生物学教研室
- Keywords:
insulin resistance;
reactive oxygen species;
melatonin;
protein kinase B;
c-Jun N-terminal kinase
- From:
The Chinese Journal of Clinical Pharmacology
2015;(20):2043-2045
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effects of melatonin ( MT) on insulin signaling transduction defect induced by linoleic acid ( LA) and the un-derlying mechanism.Methods HepG2 cells were divided into BSA group, LA group, LA+MT group and LA+VitC group cultured with va-rious agent concentrations of 10% BSA, or 0.5 mmol? L-1 LA, or 10μmol? L-1 MT plus 0.5 mmol? L-1 LA, and 1 mmol? L-1 Vitamin C plus 0.5 mmol? L-1 LA, respectively for 24h.The level of intracellular ROS was measured by fluorometry.Phosphorylation levels of protein ki-nase B ( PKB) , Forkhead box O1 ( FoxO1 ) , and c-Jun N-terminal kinase ( JNK) were determined in total cell lysates by Western-blotting with insulin stimulation.Results ROS level increased significantly in LA group compared with that in BSA group, and was significantly higher compared with that in LA +MT group ( P <0.05 ) . There was no significant difference in ROS level between LA+MT group and BSA group.Compared with LA group, the production of ROS in LA+VitC group decreased, but significantly higher than that in LA+MT group ( P<0.05 ) .Compared with BSA group, the phosphorylation levels of both PKB and FoxO1 in LA group significantly decreased, whereas, phospho-rylation level of JNK increased significantly ( P<0.05 ) .Copared with LA group, phosphorylation levels of PKB and FoxO1 in LA +MT group increased significantly, whereas, phosphorylation level of JNK significantly decreased (P<0.05).Conclusion LA causes the increased production of ROS in HepG2 cells.MT treatment can clear the excessive LA-induced ROS, reduce the activation of c-Jun amino terminal kinase and repair the impaired insulin downstream signal.
