a mouse orthologue of human CYP2A6, was also induced by ethanol in a CYP2E1-dependent manner (Lu et al., 2011). By comparing alcoholic fatty liver disease in Cyp2a5 knockout (Cyp2a5−/−) mice and the corresponding wild-type mice (Cyp2a5+/+), we found that, in contrast to CYP2E1, CYP2A5 does not contribute to the development of alcoholic fatty liver disease but actually can be protective (Hong et al., 2015). CYP2A5 induction by ethanol is regulated by the redox sensitive transcriptional factor nuclear factor-erythroid 2-related factor 2 (NRF2) (Lu et al., 2012). NRF2 signaling usually protects against oxidative injury via regulating a panel of antioxidant genes (Cederbaum, 2009) and NRF2 protects against alcoholic fatty liver disease in mice (Lamlé et al., 2008). Therefore, CYP2A5 might be among the panel of NRF2-regulated antioxidants and its protective effect on alcoholic fatty liver disease might be associated with its antioxidant action. But further study is still needed to address the exact mechanisms by which alcoholic fatty liver disease is enhanced in Cyp2a5−/− mice.
