title: Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury in mice.
abstract: OBJECTIVE
  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-deficient 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.
  
  
  CONCLUSIONS
  Recql5 protects the liver against LPS/D-Gal-induced injury through suppression of hepatocyte apoptosis and oxidative stress and modulation of CYP450 expression.
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Wan-Qin
authors.initials: WQ
authors.lastname: Liao
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Ya-Lei
authors.initials: YL
authors.lastname: Qi
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Dong
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Chao-Dong
authors.initials: CD
authors.lastname: Ding
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Liang
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Lu
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Li
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Guang-Bin
authors.initials: GB
authors.lastname: Luo
authors.affiliation: Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
authors.forename: Xin-Cheng
authors.initials: XC
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005688:Galactosamine; D022781:Hepatocytes / Q000201:enzymology* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D018384:Oxidative Stress; D010766:Phosphorylation; D053484:RecQ Helicases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C440499:lipopolysaccharide, Escherichia coli O111 B4; D005688:Galactosamine; D003577:Cytochrome P-450 Enzyme System; D048049:Extracellular Signal-Regulated MAP Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D053484:RecQ Helicases; C501069:Recql5 protein, mouse
keywords: Apoptosis; CYP450; Liver injury; Oxidative stress; Recql5