Heme oxygenase-1 as a potential therapeutic target for hepatoprotection.
Heme oxygenase (HO), the rate limiting enzyme in the breakdown of heme into carbon monoxide (CO), iron and bilirubin, has recently received overwhelming research attention. To date three mammalian HO isozymes have been identified, and the only inducible form is HO-1 while HO-2 and HO-3 are constitutively expressed. Advances in unveiling signal transduction network indicate that a battery of redox-sensitive transcription factors, such as activator protein-1 (AP-1), nuclear factor-kappa B (NF-kappaB) and nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases including mitogen-activated protein kinases play an important regulatory role in HO-1 gene induction. The products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression contributes to protection against liver damage induced by several chemical compounds such as acetaminophen, carbon tetrachloride and heavy metals, suggesting HO-1 induction as an important cellular endeavor for hepatoprotection. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect against chemically-induced liver injury as well as hepatocarcinogenesis.
Farombi
Ebenezer Olatunde
EO
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Surh
Young Joon
YJ
D000777:Anesthetics / Q000633:toxicity; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D064420:Drug-Related Side Effects and Adverse Reactions; D004790:Enzyme Induction; D005737:Garlic / Q000737:chemistry; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D019216:Metals, Heavy / Q000633:toxicity; D011719:Pyrazines / Q000494:pharmacology; D015398:Signal Transduction; D013871:Thiones; D013876:Thiophenes
D000777:Anesthetics; D019216:Metals, Heavy; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz; D051547:Heme Oxygenase-1