Effect and mechanism of heme oxygenase-1 and its reaction products of heme degradation on liver diseases / 中国药理学与毒理学杂志

ABSTRACT

Heme oxygenases (HO) are rate-limiting enzymes which degrade heme into carbon monoxide,biliverdin and free iron. HO-1 is the inducible form of HO. Induction and over-expression of HO-1 or inhibition of HO-1 degradation have been shown to interfere with replication of hepatitis B and C viruses,acute and chronic liver inflammation,and progression to fibrosis. HO-1 as well as its reaction products of heme degradation has been linked to cytoprotection by its anti-inflammatory,antioxidative and anti-apoptotic effects,displayed a broad range of protective effects against hepatic damage,and showed beneficial effects on ischemia-reperfusion injury,acute/chronic graft rejection and graft survival rate in liver transplantation. However,HO-1 has been found to be over-expressed in tumor cells. Inhibition of HO-1 expression can promote tumor cell apoptosis,decrease growth of HCC and reduce angiogenesis, suggesting that HO-1 is a potential target in the treatment of hepatic cancer. To validate the target property of HO-1,this review analyzed the effects and mechanism of action of HO-1 and its products in viral hepatitis,liver injury,hepatic fibrosis,liver transplantation and hepatocellular carcinoma. Given HO-1′s marked anti-viral,anti-inflammatory and hepatoprotective properties,the inhibitory effect of its down-modulation on hepatic cancer and the strategy to target HO-1 may promise new areas in both drug development and clinical therapy of liver diseases.