Human Gene Set: ZAMORA_NOS2_TARGETS_UP

For the Mouse gene set with the same name, see ZAMORA_NOS2_TARGETS_UP

Standard name ZAMORA_NOS2_TARGETS_UP
Systematic name M1507
Brief description Up-regulated in hepatocytes upon expression of NOS2 [GeneID=4843].
Full description or abstract Nitric oxide (NO) can modulate numerous genes directly; however, some genes may be modulated only in the presence of the inflammatory stimuli that increase the expression of the inducible nitric oxide synthase (iNOS). One method by which to examine changes in NO-mediated gene expression is to carry out a gene array analysis on NO-nai;ve cells. Herein, we report a gene array analysis on mRNA from iNOS-null (iNOS(-/-)) mouse hepatocytes harvested from mice exposed to NO by infection with an adenovirus expressing human iNOS (Ad-iNOS). Of the 6500 genes on this array, only approximately 200 were modulated either up or down by the increased iNOS activity according to our criteria for significance. Several clearly defined families of genes were modulated, including genes coding for proinflammatory transcription factors, cytokines, cytokine receptors, proteins associated with cell proliferation and cellular energetics, as well as proteins involved in apoptosis. Our results suggest that iNOS has a generally anti-inflammatory and anti-apoptotic role in hepatocytes but also acts to suppress proliferation and protein synthesis. The expression of iNOS results in increased expression of stress-related proteins, including heme oxygenase-1 (HO-1). We used HO-1 to confirm that a significant change identified by an analysis could be demonstrated as significant in cells and tissues. The elevation of HO-1 was confirmed at the protein level in hepatocytes in vitro. Furthermore, iNOS(-/-) mice experienced greatly increased liver injury subsequent to intestinal ischemia/reperfusion injury, associated with an inability to upregulate HO-1. This is the first study to address the global gene changes induced by iNOS in any cell type, and the findings presented herein may have clinical relevance for conditions such as septic or hemorrhagic shock in which hepatocytes, NO, and HO-1 play a crucial role.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12381414   Authors: Zamora R,Vodovotz Y,Aulak KS,Kim PK,Kane JM 3rd,Alarcon L,Stuehr DJ,Billiar TR
Exact source Table 1, 3-14: Increase
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Source species Mus musculus
Contributed by John Newman (University of Washington)
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identifier namespace		 MOUSE_SEQ_ACCESSION
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Version history 3.1: First introduced

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