Effect of endotoxin pretreatment-induced glycogen synthase kinase-3 inhibition on glycogen metabolism in rat liver and the mechanism
- VernacularTitle:脂多糖预处理导致的糖原合成酶激酶-3抑制对肝糖原的影响和机制
- Author:
Xiaole CHEN
1
;
Jianping GONG
;
Faliang XU
Author Information
1. 重庆市肿瘤研究所//重庆市肿瘤医院乳腺疾病中心
- Keywords:
glycogen synthase kinase-3;
glycogen metabolism;
endotoxin;
lipopolysaccharide;
liver injury;
lithium chloride;
organ protection
- From:
Journal of Southern Medical University
2014;(2):201-205
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the changes in the functional activity of glycogen synthase kinase-3 (GSK-3) in the hepatic tissue after endotoxin (lipopolysaccharide, LPS) tolerance and explore the effects of LPS-induced GSK-3 inhibition on glycogen metabolism in the liver. Methods Male SD rats were randomly divided into normal control, endotoxin pretreatment and GSK-3 inhibitor (lithium chloride) groups with corresponding pretreatments prior to a large dose of LPS challenge (10 mg/kg) to induce liver injury. Glycogen deposition and content in the hepatic tissue was detected using periodic acid-Schiff (PAS) staining and a glycogen quantification kit, respectively. Western blotting was performed for semi-quantitative analysis of protein level and inhibitory phosphorylation of GSK-3, and a Coomassie brilliant blue G-250-based colorimetric assay was used to detect calpain activity in the liver. Results Glycogen content in the liver decreased significantly after LPS challenge in all the 3 groups (P<0.05) but showed no significant difference among the groups (P>0.05). Both LPS and lithium chloride pretreatments caused a significant increase of liver glycogen content (P<0.05). LPS pretreatment induced inhibitory phosphorylation of GSK-3β (P<0.05) and partial cleavage of GSK-3α but did not affect the expression of GSK-3 protein (P>0.05). Large-dose LPS challenge significantly increased the activity of calpain in the liver tissue (P<0.05) to a comparable level in the 3 groups (P>0.05). Conclusion Endotoxin pretreatment induces inhibitory phosphorylation of GSK-3β and partial cleavage of GSK-3α and promotes the deposition of liver glycogen but does not affect the activity of calpain, which may contribute to an increased glycogen reserve for energy supply in the event of large-dose LPS challenge.