| First Author | Mamiya T | Year | 2008 |
| Journal | Tohoku J Exp Med | Volume | 216 |
| Issue | 4 | Pages | 331-9 |
| PubMed ID | 19060448 | Mgi Jnum | J:262877 |
| Mgi Id | MGI:6162207 | Doi | 10.1620/tjem.216.331 |
| Citation | Mamiya T, et al. (2008) Hepatocyte-specific deletion of heme oxygenase-1 disrupts redox homeostasis in basal and oxidative environments. Tohoku J Exp Med 216(4):331-9 |
| abstractText | Heme oxygenase-1 (HO-1) is the rate-limiting enzyme of heme catabolism and has been assumed to be important in cellular response against oxidative stress through modification of the pro-oxidant heme into less toxic catabolites that behave as antioxidants. However, the precise mechanisms involved and the physiological significance of such activity remain to be clarified. To elucidate roles HO-1 plays in vivo, hepatocyte-specific conditional knockout (CKO) mice of HO-1 gene were generated by site-specific recombination using albumin-promoter-driven Cre-loxP system. In livers of HO-1 CKO mice HO-1 protein level decreased to approximately 30% of control mouse livers. The HO-1 CKO mice are viable, exhibit normal growth curves over six months, and show no histological and serological abnormalities. We found that several cytoprotective genes, such as NAD(P)H dehydrogenase quinone 1 and glutathione S-transferase P1, showed markedly elevated expression, suggesting the increase of oxidative stress in HO-1 CKO mice even under quiescent conditions. In vivo electron paramagnetic resonance studies demonstrated that signal decay times of nitroxyl radicals were significantly longer in livers of HO-1 CKO mice than that of control mice, indicating that radical scavenging activity was significantly compromised in the mutant liver. HO-1 CKO mice were susceptible to carbon tetrachloride hepatotoxicity. These results provide the first in vivo evidence that HO-1 acts to protect cells against the oxidative stress in both basal conditions and upon chemical insult. |
