Heme oxygenase 1 protects ethanol-administered liver tissue in Aldh2 knockout mice

作者：Matsumoto Akiko^*; Thompson David; Chen Ying; Vasiliou Vasilis; Kawamoto Toshihiro; Ichiba Masayoshi

来源：Alcohol, 2016, 52: 49-54.

DOI：10.1016/j.alcohol.2016.02.004

• ALDH2
• CYP2E1
• HO-1
• Oxidative stress
• Polymorphism

A genetic polymorphism of the aldehyde dehydrogenase 2 (ALDH2) gene, ALDH22, 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-alpha) 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 I (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 LDH22. Our continued studies support the epidemiological finding that possession of ALDH22 is a protective factor in the liver of the healthy individual.

• 出版日期2016-5