Heme oxygenase

• OMIM: 141250
• UniProt: P09601

Heme oxygenase ( Hmox ) the name of the enzyme, the heme is oxidized to iron ( in the form of Fe3 ions), biliverdin and carbon monoxide and degrades. Occur in mammals present in the microsomes of the cells, but also in cyanobacteria and red algae. Mutations at Hmox gene in humans can very rarely cause heme oxygenase deficiency. The enzyme is not only essential for the porphyrin degradation but is also involved in signal transduction.

Heme oxygenase exists in mammals in up to three isoforms in humans in two, the inducible isoform of heme oxygenase -1 ( HO -1) and constitutive isoform heme oxygenase -2 ( HO -2). Heme oxygenase -1 is a protein with a molecular mass of 32 kDa. Heme oxygenase -1 is upregulated in tissues of mammals, by a large number of stimuli, such as TGF- β, platelet -derived growth factor (PDGF), Vascular Endothelial Growth Factor (VEGF), Stromal cell-derived factor 1 ( SDF -1), NO, peroxynitrite, lipid peroxides, oxygen deficiency ( hypoxia), oxidative stress, cytokines, and others. Heme oxygenase -2 is constitutively, that is independent of internal and external factors in brain endothelial and testicular formed ( expressed). The degradation of heme by the heme oxygenase system is the main source for the formation of carbon monoxide in the body.

Biological Significance

Heme oxygenase -1 and the metabolic product carbon monoxide take in the body performs important functions: they promote the formation of new vessels ( proangiogenic effect ) and inhibit inflammation ( anti-inflammatory activity ), oxidative stress ( antioxidant effect ), increased connective tissue ( antifibrotic effect ) and programmed cell death ( anti-apoptotic effect ). VEGF and SDF -1 exert their proangiogenic effect by the fact that they induce heme oxygenase.

HO-1 in the intestinal mucosa from the building with the food taken heme.

Medical importance

Embryonic development

In embryonic development is the formation of new vessels, and so that the heme oxygenase / carbon monoxide system critical. In the pre-eclampsia, the concentration is reduced from the heme oxygenase -1 in the placenta, in the affected pregnancy the concentration is reduced to carbon monoxide in the exhaled air. Smokers who have an increased concentration of carbon monoxide in blood, suffer less from pre-eclampsia. Heme oxygenase -1 and carbon monoxide inhibit the release of pre-eclampsia anti-angiogenic mediators such as Soluble fms -like tyrosine kinase -1 ( sFlt1 ) and Soluble endoglin ( sEng ).

Tumor angiogenesis

Various tumors, including renal cell carcinoma and prostate cancer express high levels of heme oxygenase -1. Heme oxygenase promotes neovascularization in tumors and inhibits programmed cell death of tumor cells. In animal models, inhibition of heme oxygenase leads to a decrease of tumor growth.

Wound healing

Prerequisite for wound healing is the formation of new blood vessels ( neovascularization ). Mice with reduced formation of heme oxygenase - 1 have impaired wound healing.

Connective tissue

Heme oxygenase -1 inhibits a pathological increase in connective tissue (fibrosis). Mice with reduced formation of heme oxygenase - 1 have disability of Harnabflusses ( urinary tract obstruction ) in the affected kidney an increased fibrosis, increased expression of TGF- β1, an enhanced inflammatory response and an increased transition of epithelial cells in connective tissue cells ( epithelial -mesenchymal transition (EMT ) ) on. Induction of heme oxygenase -1 by hemin inhibits renal fibrosis via an antiapoptotic pathway; Zinc protoporphyrin, an inhibitor of heme oxygenase -1, this antifibrotic effect cancels partially.