Endoplasmic reticulum stress promote hepatocyte apoptosis by mediating glycogen synthase kinase 3β
10.3760/cma.j.issn.0254-5101.2012.07.011
- VernacularTitle:内质网应激介导糖原合成酶激酶-3β促进肝细胞凋亡
- Author:
Bingzhang YANG
;
Feng REN
;
Tao WEN
;
Zhengfu PIAO
;
Sujun ZHENG
;
Jing ZHANG
;
Yu CHEN
;
Dexi CHEN
;
Zhongping DUAN
;
Shuisheng SHI
- Publication Type:Journal Article
- Keywords:
Endoplasmic reticulum;
Stress;
Apoptosis;
Glycogen synthase kinase 3β
- From:
Chinese Journal of Microbiology and Immunology
2012;32(7):617-621
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze the role of a key intracellular signaling molecule GSK3β in hepatocyte apoptosis induced by endoplasmic reticulum stress (ERS).Methods Using mouse hepatoma cell lines(Hepa 1) as cell apoptosis model triggered by tunicamycin,an endoplasmic reticulum stress inducer.One hour before Hepa 1 apoptosis induced by tunicamycin,SB216763 specifically inhibited the activity of GSK3β.Living cells/apoptotic cells were detected using acetoxymethyl (AM)/propidium iodide (PI) staining; Furthermore,the measurement of lactate dehydrogenase(LDH) of cell culture supernatant to evaluate the apoptosis.We detect p-GSK3β,GSK3β,the ERS-related protein(GRP78,CHOP and caspase-12) and caspase-3,cleaved caspase-3 protein expression using Western blot.Results Endoplasmic reticulum stress induced by tunicamycin promotes GSK3β activity; Inhibition of GSK3β activity alleviates endoplasmic reticulum stress:the expression of GRP78,CHOP and caspase-12 expression are inhibited.At the same time,GSK3β activity inhibition significantly reduced the endoplasmic reticulum stress-induced apoptosis:compared to cell apoptosis model group,the intervention group of SB216763 showed that the level of LDH decreased significantly,and PI staining of apoptotic cells was also significant reduction.Western blot results showed that the inhibition of GSK 3 β activity reduced reactive cleaved caspase-3 protein.Conclusion GSK3β is an important signaling molecule in the apoptosis pathway induced by endoplasmic reticulum stress ;Endoplasmic reticulum stress promotes hepatocyte apoptosis by mediating GSK3β.
