A Review on Hemeoxygenase-2: Focus on Cellular Protection and Oxygen Response
Physiological roles of HO-2 enzymatic activity products. Heme is cleaved by HO-2 producing equimolar amounts of CO, Fe2+, and BV. Enzymatic reaction requires NADPH, Cyt P450, and O2. CO has antiapoptotic, antiproliferative, and anti-inflammatory activities through p38/MAPK processes. CO also regulates vascular tone via cGC/cGMP, stabilization of HIF-1α and inhibits NADPH oxidase and NOS. BV is metabolized to BR by NAD(P)H : BVR. Fe2+ is sequestered by ferritin but also can form DNIC, a complex with protective effects through inhibition of caspases activity. BVR: biliverdin reductase; cGC: guanylate cyclase; DNIC: iron-sulfur cluster dinitrosyl iron-sulfur complex; HIF-1α: alfa subunit of Hypoxia inducible factor-1; NO: nitric oxide; and NOS; nitric oxide synthase.
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