Modulations of Histone Deacetylase 2 Offer a Protective Effect through the Mitochondrial Apoptosis Pathway in Acute Liver Failure

• Published in: Oxidative medicine and cellular longevity 2019-01, Vol.2019 (2019), p.1-17
• Main Authors: Gong, Zuo-Jiong, Zhang, Wen-Bin, Chen, Qian, Jiao, Fang-Zhou, Yang, Fan, Wang, Yao, Wang, Lu-Wen
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Cancer; Cytochrome; Cytochrome c; Flow cytometry; Galactosamine - metabolism; Histone Deacetylase 2 - antagonists & inhibitors; Histone Deacetylase 2 - metabolism; Histones - metabolism; Homeostasis; Lipopolysaccharides - pharmacology; Liver; Liver failure; Liver Failure, Acute - chemically induced; Liver Failure, Acute - metabolism; Medical research; Mitochondria - drug effects; Mitochondria - metabolism; Mitogens; Permeability; Proteases; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; RNA; Rodents; Signal Transduction - drug effects; Tumor necrosis factor; Tumor necrosis factor-TNF
• ISSN: 1942-0900; 1942-0994; 1942-0994
• DOI: 10.1155/2019/8173016

The purpose of this study was to investigate the modulation of histone deacetylase 2 (HDAC2) on mitochondrial apoptosis in acute liver failure (ALF). The cellular model was established with LO2 cells stimulated by tumor necrosis factor alpha (TNF-α)/D-galactosamine (D-gal). Rats were administrated by lipopolysaccharide (LPS)/D-gal as animal model. The cell and animal models were then treated by HDAC2 inhibitor CAY10683. HDAC2 was regulated up or down by lentiviral vector transfection in LO2 cells. The mRNA levels of bcl2 and bax were detected by real-time PCR. The protein levels of HDAC2, bcl2, bax, cytochrome c (cyt c) in mitochondrion and cytosol, apoptosis protease activating factor 1 (apaf1), caspase 3, cleaved-caspase 3, caspase 9, cleaved-caspase 9, acetylated histone H3 (AH3), and histone H3 (H3) were assayed by western blot. Apoptosis was detected by flow cytometry. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) levels were also assayed. The openness degree of the mitochondrial permeability transition pore (MPTP) was detected by ultraviolet spectrophotometry. The apoptosis of hepatocytes in liver tissues was determined by tunnel staining. The liver tissue pathology was detected by hematoxylin eosin (HE) staining. The ultrastructure of liver tissue was observed by electron microscopy. Compared with cell and rat model groups, the bax mRNA level was decreased, and bcl2 mRNA was increased in the CAY10683 treatment group. The protein levels of HDAC2, bax, cyt c in cytosol, apaf1, cleaved-caspase 3, and cleaved-caspase 9 were decreased, and the apoptosis rate was decreased (P