TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000216117
  • Gene Name:HMOX1
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:NA
  • mRNA Pathway:PPARG signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB00641
  • Drug Name:Simvastatin
  • Drug Method:up-regulated the gene expression

Disease basic infommation

  • Disease:cardiovascular disease
  • Tissue:cell line HUVEC

Other information

  • Title:Simvastatin-dependent up-regulation of heme oxygenase-1 via mRNA stabilization in human endothelial cells
  • Journal:European Journal of Pharmaceutical Sciences
  • Published:2010
  • PubMed ID:20594940
  • Abstract:Heme oxygenase (HO)-1, which is the inducible isoform of the rate-limiting enzyme of heme degradation, has potent antioxidant and anti-inflammatory effects and is an emerging therapeutic target for the treatment of cardiovascular disease. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also termed statins, induce HO-1 gene expression in endothelial cells, but the underlying regulatory mechanisms are not well studied. To further investigate the statin-specific HO-1 regulation, we examined HO-1 gene expression by simvastatin in cell cultures of human endothelial cells. Simvastatin-dependent HO-1 gene activation was significantly reduced by pharmacological inhibition of the p38 MAPK and phosphotidylinositol-3-kinase (PI3K)/Akt pathways. Although HO-1 is considered to be primarily regulated at the transcriptional level, simvastatin induced activity of a human HO-1 promoter gene construct only to a minor extent. By contrast, studies with actinomycin D indicated that the half-life of HO-1 mRNA was significantly prolonged in the presence of simvastatin suggesting a post-transcriptional mode of HO-1 regulation. The increased HO-1 mRNA stability by this compound was blocked by inhibition of PI3K/Akt, but not by that of p38 MAPK. In conclusion, statin-dependent up-regulation of endothelial HO-1 is mainly regulated by stabilization of HO-1 mRNA via a PI3K/Akt-dependent signaling pathway.
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