Endoplasmic reticulum stress mediates lipopolysaccharide-induced apoptosis in rat hepatocyte

• Published in: Fa yi xue za zhi Vol. 30; no. 1; p. 13
• Main Authors: Ji, Ying-Lei, Yan, Jun, Wang, Yan-Sha, Liu, Yi-Chang, Gu, Zhen-Yong
• Format: Journal Article
• Language: Chinese
• Published: China 01.02.2014
• Subjects: Animals; Apoptosis; Caspase 3; Cell Survival; Endoplasmic Reticulum Stress; Heat-Shock Proteins; Hepatocytes; Lipopolysaccharides; Phenylbutyrates; Rats
• ISSN: 1004-5619
• DOI: 10.3969/j.issn.1004-5619.2014.01.003

To investigate the role of endoplasmic reticulum stress (ERS) in lipopolysaccharide (LPS)-induced hepatocyte apoptosis. Cells of the rat hepatocyte line BRL were cultured. The hepatocytes were treated with LPS, ERS inducer thapsigargin (TG), and ERS inhibitor 4-phenylbutyric acid (4-PBA), respectively or in their different combination. The cell viability was measured by MTT assay. The cyto-nuclear morphological changes of apoptosis cells were detected by the fluorescent dye Hoechst 33258. The apoptosis rate was assessed by flow cytometry with Annexin V-FITC/PI double-staining. Expressions of GRP78 as ERS marker protein, CHOP, caspase-12 and cleaved-caspase-3 as ERS related protein were detected by Western blotting. LPS could cause a decrease in cell viability and an increase in apoptosis rate in a dose- and time-dependent manner. The expression of GRP78, CHOP, caspase-12 and cleaved-caspase-3 proteins were significantly increased with LPS treatment. TG led to a marked decrease in cell viability and an increase in apoptosis rate, which aggravated the hepatocyte injury induced by LPS; whereas 4-PBA alleviated LPS-induced apoptosis. ERS mediates LPS-induced hepatocyte injuries, indicating that ERS may play a vital role in the pathogenesis of LPS-induced hepatocyte injuries.