Effect and Mechanism of Celastrol on Endoplasmic Reticulum Stress in Hepatic L02 Cells of Nonalcoholic Fatty Liver Disease
10.13422/j.cnki.syfjx.20191303
- VernacularTitle: 雷公藤红素对非酒精性脂肪肝L02细胞内质网应激的影响及机制
- Author:
Xia JIANG
1
;
Hui-ling JIANG
1
;
Fan YANG
1
;
Ye-wei XIAO
1
;
Zhi-qiang FENG
1
;
Qiang-wen PAN
1
Author Information
1. Southwest Medical University, Luzhou 646000, China
- Publication Type:Research Article
- Keywords:
celastrol;
non-alcoholic fatty liver disease;
endoplasmic reticulum stress;
hepatic L02 cells
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2019;25(14):99-105
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect of celastrol in inhibiting the lipid metabolism disorder in hepatic L02 cells and its possible mechanism on endoplasmic reticulum stress (ERS) of non-alcoholic fatty liver cells by intervening non-alcoholic fatty liver disease(NAFLD) cell model with celastrol. Method:Hepatic L02 cells were divided into control group, model group, low-dose celastrol treatment group (Cel 0.5 mg·L-1), high-dose celastrol treatment group (Cel 1 mg·L-1) and simvastatin group (SIM 6 mg·L-1) for cultivation. The contents of total cholesterol (TC) and total triglyceride (TG) in hepatic L02 cells were detected, and the oil red staining was used to detected the lipid accumulation in hepatic L02 cells. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to detect the mRNA and protein expression levels of endoplasmic reticulum stress (ERS)-related signal molecules activating transcription factor 6 (ATF6), glucose regulated protein 78 (GRP78), inositol-requiring enzyme 1 (IRE1), sterol regulatory element-binding protein cleavage-activating protein (SCAP), sterol regulatory element-binding protein-1c (SREBP-1c) and sterol regulatory element-binding protein-2 (SREBP-2) in hepatic L02 cell model respectively. Result:The contents of TC and TG in hepatic L02 cells of NAFLD group were significantly higher than those in control group (P<0.05). The TC and TG contents in hepatic L02 cells of Cel 0.5 mg·L-1 group, Cel 1 mg·L-1 group and SIM 6 mg·L-1 group were significantly lower than those in NAFLD group (P<0.05). Oil red O staining showed that a large amount of red-stained lipid particles were deposited in the hepatic L02 cells of the NAFLD group, while the red-stained lipid particles in the Cel 0.5 mg·L-1 group, the Cel 1 mg·L-1 group, and the SIM 6 mg·L-1 group were lower than the NAFLD group to different degrees. According to the results of RT-PCR and Western blot, the mRNA transcription and protein expression levels of ERS-related signaling molecules ATF6, GRP78, IRE1, SCAP, SREBP-1c and SREBP-2 in hepatic L02 cells of NAFLD group were higher than those of control group (P<0.05). The mRNA transcription and protein expression levels of ERS-related signaling molecules ATF6, GRP78, IRE1, SCAP, SREBP-1c and SREBP-2 in hepatic L02 cells of Cel 0.5 mg·L-1 group, Cel 1 mg·L-1 group and SIM 6 mg·L-1 group were lower than those of NAFLD group (P<0.05). There was no significant difference in the mRNA transcription and protein expression levels of ATF6, GRP78, IRE1, SCAP, SREBP-1c and SREBP-2 between the Cel 1 mg·L-1 group and the SIM 6 mg·L-1 group. Conclusion:Celastrol can reduce the lipid metabolism disorder in hepatic L02 cells by down-regulating the expressions of ERS-related signaling molecules ATF6, GRP78, IRE1, SCAP, SREBP-1c and SREBP-2 in hepatic L02 cells, so as to improve NAFLD.
