title: The Protective Effects of Helix B Surface Peptide on Experimental Acute Liver Injury Induced by Carbon Tetrachloride.
abstract: To investigate the protective effects of helix B surface peptide (HBSP) on acute liver injury induced by carbon tetrachloride (CCl4).
  
  
  
  HBSP (8 nmol/kg) was intraperitoneally injected into C57 BL/6 mice 2 h after CCl4administration. Serum and liver tissue samples were collected 24 h after injury. Liver function and histological injuries were evaluated. Inflammatory cell infiltration and cytokines were examined and hepatocytes apoptosis was measured. The human liver cell line LO2 and murine primary hepatocytes were stimulated by CCl4with and without HBSP treatment and glutathione peroxidase activity, cell survival, and apoptosis were evaluated. In addition, we examined the PI3K/Akt/mTORC1 pathway to elucidate the mechanism underlying HBSP-mediated protection in acute liver injury.
  
  
  
  HBSP significantly decreased serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and pro-inflammatory cytokines in liver tissues after CCl4injection compared with those in the control group. Immunohistochemical staining indicated that the number of CD3-, CD8-, and CD68-positive cells and the expression of cleaved caspase-3 were significantly decreased by HBSP treatment. Additionally, HBSP reduced apoptosis in vivo. In an in vitro study, the glutathione peroxidase activity and survival rate increased, while the total apoptotic rate was reduced in the HBSP-treated group compared with that in the control group after CCl4treatment. HBSP activated the PI3K/Akt/mTORC1 pathway, which was confirmed by the PI3K inhibitor LY294002 both in vivo and in vitro. Furthermore, HBSP increased the survival of mice with acute liver injury, and this effect was abolished by LY294002.
  
  
  
  HBSP is a potential therapeutic agent against acute liver injury induced by CCl4.
authors.affiliation: Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Shanghai Institute of Liver Diseases, Shanghai, 200032, China.
authors.forename: Shengdi
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.|Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Respiration, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Nuo
authors.initials: N
authors.lastname: Xu
authors.affiliation: Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.|Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Shanghai Institute of Liver Diseases, Shanghai, 200032, China.
authors.forename: Jiyao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. xizhongshen@126.com.|Department of Internal Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. xizhongshen@126.com.|Shanghai Institute of Liver Diseases, Shanghai, 200032, China. xizhongshen@126.com.|Key Laboratory of Medical Molecule Virology, Ministry of Education and Health, Shanghai, 200032, China. xizhongshen@126.com.
authors.forename: Xizhong
authors.initials: X
authors.lastname: Shen
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D017252:CD3 Complex / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D002867:Chromones / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D022781:Hepatocytes; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D046912:Multiprotein Complexes / Q000378:metabolism; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D000410:Alanine Transaminase; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001219:Aspartate Aminotransferases; D017252:CD3 Complex; D016827:CD8 Antigens; D002251:Carbon Tetrachloride; D002867:Chromones; D016207:Cytokines; D004791:Enzyme Inhibitors; D004921:Erythropoietin; D005979:Glutathione Peroxidase; D007770:L-Lactate Dehydrogenase; D000076222:Mechanistic Target of Rapamycin Complex 1; D009025:Morpholines; D046912:Multiprotein Complexes; D010446:Peptide Fragments; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C585201:glutaminyl-glutamyl-glutaminyl-leucyl-glutamyl-arginyl-alanyl-leucyl-asparagyl-seryl-serine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: Acute liver injury; Apoptosis; Helix B surface peptide; Inflammation