Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury in mice

Autor: Chao Dong Ding, Xin Cheng Lu, Guang Bin Luo, Wan Qin Liao, Ya Lei Qi, Li Ting Lu, Wen Feng Li, Tao Xu, Lin Wang, He Li, Rui Liu, Weicheng Liang, Xiao Ming Dong
Rok vydání: 2015
Předmět:
Lipopolysaccharides
Male
Time Factors
Aspartate transaminase
Apoptosis
Galactosamine
medicine.disease_cause
Superoxide dismutase
chemistry.chemical_compound
Cytochrome P-450 Enzyme System
Medicine
Animals
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
chemistry.chemical_classification
Liver injury
Mice
Knockout
biology
RecQ Helicases
business.industry
Caspase 3
Glutathione peroxidase
Gastroenterology
General Medicine
Basic Study
Malondialdehyde
medicine.disease
Molecular biology
Nitric oxide synthase
Mice
Inbred C57BL
Disease Models
Animal
Oxidative Stress
Biochemistry
chemistry
Alanine transaminase
Liver
Neutrophil Infiltration
biology.protein
Hepatocytes
Cytokines
Chemical and Drug Induced Liver Injury
Inflammation Mediators
business
Oxidative stress
DNA Damage
Signal Transduction
Zdroj: World journal of gastroenterology. 21(36)
ISSN: 2219-2840
Popis: AIM: To investigate the effects of Recql5 deficiency on liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-Gal). METHODS: Liver injury was induced in wild type (WT) or Recql5-deficient mice using LPS/D-Gal, and assessed by histological, serum transaminases, and mortality analyses. Hepatocellular apoptosis was quantified by transferase dUTP nick end labeling assay and Western blot analysis of cleaved caspase-3. Liver inflammatory chemokine and cytochrome P450 expression was analyzed by quantitative reverse transcription-PCR. Neutrophil infiltration was evaluated by myeloperoxidase activity. Expression and phosphorylation of ERK, JNK, p65, and H2A.X was determined by Western blot. Oxidative stress was evaluated by measuring malondialdehyde production and nitric oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activity. RESULTS: Following LPS/D-Gal exposure, Recql5-deficient mice exhibited enhanced liver injury, as evidenced by more severe hepatic hemorrhage, higher serum aspartate transaminase and alanine transaminase levels, and lower survival rate. As compared to WT mice, Recql5-deficient mice showed an increased number of apoptotic hepatocytes and higher cleaved caspase-3 levels. Recql5-deficient mice exhibited increased DNA damage, as evidenced by increased γ-H2A.X levels. Inflammatory cytokine levels, neutrophil infiltration, and ERK phosphorylation were also significantly increased in the knockout mice. Additionally, Recql5-deficicent mice exhibited increased malondialdehyde production and elevated inducible nitric oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activity, indicative of enhanced oxidative stress. Moreover, CYP450 expression was significantly downregulated in Recql5-deficient mice after LPS/D-Gal treatment. CONCLUSION: Recql5 protects the liver against LPS/D-Gal-induced injury through suppression of hepatocyte apoptosis and oxidative stress and modulation of CYP450 expression.
Databáze: OpenAIRE
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