Hemorrhagic shock induces differential gene expression and apoptosis in mouse liver.
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.
Sundar
Shirin V
SV
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Li
Ying-Yue
YY
Rollwagen
Florence M
FM
Maheshwari
Radha K
RK
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
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