title: Heme oxygenase 1 protects ethanol-administered liver tissue in Aldh2 knockout mice.
abstract: A genetic polymorphism of the aldehyde dehydrogenase 2 (​ALDH2) gene, ALDH2*2, encodes an enzymatically defective ALDH2 protein. Recent epidemiological studies suggest that possessing ALDH2*2 is a protective factor for liver tissue in healthy individuals, although these studies lack a mechanistic explanation. Our animal studies have shown the same trend: levels of serum alanine transaminase (ALT), hepatic malondialdehyde (MDA), and hepatic tumor necrosis factor alpha (TNF-α) were lower in Aldh2 knockout (Aldh2(-/-)) mice than in wild-type (Aldh2(+/+)) mice after ethanol administration. To propose a mechanistic hypothesis, residual liver specimens from the previous experiment were analyzed. An anti-oxidative protein, heme oxygenase 1 (HO-1), and an oxidative stress-producing protein, cytochrome P450 2E1 (CYP2E1), were detected at higher levels in Aldh2(-/-) mice than in Aldh2(+/+) mice, regardless of ethanol treatment. Other oxidative stress-related proteins and inflammatory cytokines did not show such a significant difference. To conclude, we propose a protective role of HO-1 in individuals with A​LDH2*2. Our continued studies support the epidemiological finding that possession of ALDH2*2 is a protective factor in the liver of the healthy individual.
authors.affiliation: Department of Social Medicine, Saga University School of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan. Electronic address: matsumoa@cc.saga-u.ac.jp.
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Department of Clinical Pharmacy, University of Colorado School of Pharmacy, 12850 E. Montview Blvd., Aurora, CO 80045, USA.
authors.forename: David
authors.initials: D
authors.lastname: Thompson
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado School of Pharmacy, Aurora, CO 80045, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado School of Pharmacy, Aurora, CO 80045, USA.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Vasiliou
authors.affiliation: Department of Environmental Health, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, Fukuoka 807-0804, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kawamoto
authors.affiliation: Department of Social Medicine, Saga University School of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Ichiba
mesh_terms: D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000172:deficiency*; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D018836:Inflammation Mediators / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D018836:Inflammation Mediators; D008565:Membrane Proteins; D000431:Ethanol; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C515029:ALDH2 protein, mouse; D000071396:Aldehyde Dehydrogenase, Mitochondrial
keywords: ALDH2; CYP2E1; HO-1; Oxidative stress; Polymorphism