title: Hemorrhagic shock induces differential gene expression and apoptosis in mouse liver.
abstract: Comprehensive knowledge of the gene expression changes induced by hemorrhage in vital organs will greatly improve prognosis and therapy. Therefore, we used a mouse model of non-resuscitated hemorrhagic shock to study the pattern of stress-induced genes in liver at 1, 4, and 24 h following surgery. Hepatic injury was confirmed by assessment of liver injury markers and apoptotic cell death. We found that a variety of stress-regulated genes were differentially expressed, including seven genes that have not been reported previously as being regulated by hemorrhagic shock: ATF-2, alphaB-crystallin, GADD45, GADD45beta, Mdm2, p21Waf1, and TRPM-2. The changes in mRNA levels of the transcription factors AP-1, Egr-1, HSF-1, and NF-kappaB were transient but protein expression was noticeable at later time points. Our findings show that oxidative stress causes immediate upregulation of genes involved in a variety of cellular defense pathways. Complex interactions among them might determine the ultimate fate of the cell.
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Shirin V
authors.initials: SV
authors.lastname: Sundar
authors.forename: Ying-Yue
authors.initials: YY
authors.lastname: Li
authors.forename: Florence M
authors.initials: FM
authors.lastname: Rollwagen
authors.forename: Radha K
authors.initials: RK
authors.lastname: Maheshwari
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D018797:Cell Cycle Proteins / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015227:Lipid Peroxidation; D008099:Liver / Q000293:injuries / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000235:genetics; D000097642:GADD45 Proteins
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger; D014157:Transcription Factors; D038203:alpha-Crystallin B Chain; C493957:Cdkn1a protein, mouse; C499072:Gadd45a protein, mouse; D000097642:GADD45 Proteins; C497207:Mdm2 protein, mouse