5-Hydroxymethylfurfural protects against ER stress-induced apoptosis in GalN/TNF-α-injured L02 hepatocytes through regulating the PERK-eIF2α signaling pathway.
10.1016/S1875-5364(15)30095-9
- Author:
Ze-Qun JIANG
1
;
Yan-Xia MA
1
;
Mu-Han LI
1
;
Xiu-Qin ZHAN
1
;
Xu ZHANG
2
;
Ming-Yan WANG
1
Author Information
1. Nanjing University of Chinese Medicine, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing 210023, China.
2. Nanjing University of Chinese Medicine, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing 210023, China. Electronic address: zhangxu@njucm.edu.cn.
- Publication Type:Journal Article
- Keywords:
5-Hydroxymethylfurfural;
Apoptosis;
GalN/TNF-α;
L02 hepatocytes;
PERK-eIF2α
- MeSH:
Apoptosis;
drug effects;
Cornus;
chemistry;
Endoplasmic Reticulum Stress;
drug effects;
Eukaryotic Initiation Factor-2;
genetics;
metabolism;
Furaldehyde;
analogs & derivatives;
pharmacology;
Galactosamine;
metabolism;
Hepatocytes;
cytology;
drug effects;
metabolism;
Humans;
Liver;
cytology;
drug effects;
metabolism;
Plant Extracts;
pharmacology;
Protective Agents;
pharmacology;
Signal Transduction;
drug effects;
Tumor Necrosis Factor-alpha;
genetics;
metabolism;
eIF-2 Kinase;
genetics;
metabolism
- From:
Chinese Journal of Natural Medicines (English Ed.)
2015;13(12):896-905
- CountryChina
- Language:English
-
Abstract:
5-Hydroxymethylfurfural (5-HMF), a water-soluble compound extracted from wine-processed Fructus corni, is a novel hepatic protectant for treating acute liver injury. The present study was designed to investigate the protective effect of 5-HMF in human L02 hepatocytes injured by D-galactosamine (GalN) and tumor necrosis factor-α (TNF-α) in vitro and to explore the underlying mechanisms of action. Our results showed that 5-HMF caused significant increase in the viability of L02 cells injured by GalN/TNF-α, in accordance with a dose-dependent decrease in apoptotic cell death confirmed by morphological and flow cytometric analyses. Based on immunofluorescence and Western blot assays, we found that GalN/TNF-α induced ER stress in the cells, as indicated by the disturbance of intracellular Ca(2+) concentration, the activation of protein kinase RNA (PKR)-like ER kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α), and expression of ATF4 and CHOP proteins, which was reversed by 5-HMF pre-treatment in a dose-dependent manner. The anti-apoptotic effect of 5-HMF was further evidenced by balancing the expression of Bcl-2 family members. In addition, the knockdown of PERK suppressed the expression of phospho-PERK, phospho-eIF2α, ATF4, and CHOP, resulting in a significant decrease in cell apoptosis after the treatment with GalN/TNF-α. 5-HMF could enhance the effects of PERK knockdown, protecting the cells against the GalN/TNF-α insult. In conclusion, these findings demonstrate that 5-HMF can effectively protect GalN/TNF-α-injured L02 hepatocytes against ER stress-induced apoptosis through the regulation of the PERK-eIF2α signaling pathway, suggesting that it is a possible candidate for liver disease therapy.
