title: [AMPK activator down-regulates the expression of tissue factor in fulminant hepatitis mice].
abstract: AMP activated protein kinase (AMPK) is a pivotal metabolic regulatory enzyme and novel target of controlling inflammation. Our previous studies had demonstrated that 5-amino-4-imidazolecarboxamide riboside (AICAR), an AMPK activator, attenuated lipopolysaccharide (LPS)/D-galactosamine (D-gal)-induced fulminant hepatitis via suppressing inflammatory response. Since inflammation usually activates the coagulation response and aggravates inflammation-induced tissue injury, the present study was to explore the effects of AICAR on inflammation-induced activation of coagulation. Male BALB/c mice received LPS/D-gal intraperitoneal injection were used as fulminant hepatitis model. Western blot was used to detect tissue factor (TF) and hypoxia-inducible factor 1α (HIF-1α) protein expressions in hepatic tissue, as well as nuclear factor kappa B (NF-κB) p65 translocation into the nucleus. Real-time quantitative PCR was used to analyze erythropoietin (EPO) mRNA expression level. Lactic acid (LA) level in hepatic tissue was detected by kit. The results showed that LPS/D-gal induced the enhanced expression of TF, elevation of NF-κB p65 nuclear translocation, up-regulation of HIF-1α and EPO expressions, and increased LA level. These above alterations could be suppressed by AICAR. These results suggest that AICAR may down-regulate LPS/D-gal-induced TF expression (coagulation activity), and relieve hepatic hypoxia and metabolic disorder via suppressing the activity of NF-κB, which may be a novel mechanism of the beneficial effect of AICAR on LPS/D-gal-induced fulminant hepatitis.
authors.affiliation: Hospital of Chongqing University of Arts and Sciences, Chongqing 402160, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ai
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Ge
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China.|Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. zhangli@cqmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives; D000818:Animals; D015536:Down-Regulation; D004921:Erythropoietin; D006505:Hepatitis; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007249:Inflammation; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D016328:NF-kappa B; D013925:Thromboplastin; D015854:Up-Regulation
chemical_list: C554270:EPO protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008070:Lipopolysaccharides; D016328:NF-kappa B; D004921:Erythropoietin; D000620:Aminoimidazole Carboxamide; C031340:imidazolecarboxamide; D013925:Thromboplastin; D055372:AMP-Activated Protein Kinases