Induction of heat shock protein 27 by bicyclol attenuates d-galactosamine/lipopolysaccharide-induced liver injury.
Heat shock proteins (Hsps) are critical for cell survival under adverse environmental conditions. Bicyclol is a novel hepatoprotectant that has been shown to protect against liver injury by inducing Hsps, including Hsp27 and Hsp70. Although the role of Hsp70 in protecting against acute hepatic failure has been clearly explored, the precise function of Hsp27 in this setting is poorly defined. This study was undertaken to evaluate the role of Hsp27 in bicyclol-mediated hepatoprotection. Both primary hepatocytes and bone marrow-derived macrophages were subjected to bicyclol treatment, followed by detection of Hsp27 expression. Adenoviruses containing the mouse Hsp27 coding sequence or shRNA interference sequence targeting Hsp27 were used to manipulate Hsp27 expression in the liver before the mice were treated with bicyclol and/or confronted with D-galactosamine/lipopolysaccharide (Galn/LPS)-induced acute liver damage. Only hepatocytes increased their Hsp27 expression after bicyclol treatment and the time course of bicyclol-induced Hsp27 expression in hepatocytes was in line with the in vivo results. Although high-dose bicyclol could protect against liver failure without Hsp27, the effect of bicyclol given at a low dose was dependent on Hsp27 induction. Adenovirus-mediated transduction of Hsp27 protected against acute liver damage and partially replicated the protective effect afforded by bicyclol. These results demonstrated that bicyclol induced Hsp27 expression in hepatocytes, which was essential to bicyclol-mediated hepatoprotection. Overexpression of Hsp27 in hepatocytes could confer remarkable protection against acute liver damage.
Department of Thyroid and Breast Oncological Surgery, Xuzhou Medical College Affiliated Huaian Hospital, Huaihai South Road 62#, Huaian, Jiangsu 223001, PR China.
Hui-Juan
HJ
Dai
Department of Transplantation and Hepatic Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao tong University, Dongfang Road 1630#, Shanghai 200127, PR China.
Da-Wei
DW
Li
Department of anesthesiology, Huai Yin Hospital, Beijing West Road 38#, Huaian, Jiangsu 223002, PR China.
Ya-Xiang
YX
Wang
Department of Thyroid and Breast Oncological Surgery, Xuzhou Medical College Affiliated Huaian Hospital, Huaihai South Road 62#, Huaian, Jiangsu 223001, PR China.
Ai-Jun
AJ
Sun
Department of Thyroid and Breast Oncological Surgery, Xuzhou Medical College Affiliated Huaian Hospital, Huaihai South Road 62#, Huaian, Jiangsu 223001, PR China.
Yi-Xian
YX
Lu
Department of Thyroid and Breast Oncological Surgery, Xuzhou Medical College Affiliated Huaian Hospital, Huaihai South Road 62#, Huaian, Jiangsu 223001, PR China.
Xin-
X
Ding
Department of Transplantation and Hepatic Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao tong University, Dongfang Road 1630#, Shanghai 200127, PR China.
Ming-
M
Zhang
Department of Thyroid and Breast Oncological Surgery, Xuzhou Medical College Affiliated Huaian Hospital, Huaihai South Road 62#, Huaian, Jiangsu 223001, PR China. Electronic address: syg3609@163.com.
Yong-Gang
YG
Song
Department of Thyroid and Breast Oncological Surgery, Xuzhou Medical College Affiliated Huaian Hospital, Huaihai South Road 62#, Huaian, Jiangsu 223001, PR China. Electronic address: huangxuandong1962@163.com.
Xuan-Dong
XD
Huang
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005688:Galactosamine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D001713:Biphenyl Compounds; D055551:HSP27 Heat-Shock Proteins; D008070:Lipopolysaccharides; D005688:Galactosamine; C477843:bicyclol
Acute liver failure; Bicyclol; Hepatocyte; Hsp27; Macrophage