Abstract
mice. mRNA expression of Nrf2 was increased by 80% (p<0.02 vs. nTg) while mRNA expression of its cytosolic repressor protein, Keap1, was increased by 180% (p<0.006 vs. nTg). Expression of the antioxidant enzymes CAT, HO-1, GPx, GST and TRX were significantly increased in liver of the Tg mice. Expression of SOD 1 and SOD 2 was not increased in Tg mice. Conclusion: Overexpression of CYP2E1 in hepatocytes in the setting of a high fat diet increases ER stress which leads to increased expression of Nrf2 as well as multiple antioxidant systems regulated by Nrf2. Nevertheless, markers of oxidative stress are increased in CYP2E1 Tg mice indicating insufficient overall antioxidant response. Increased expression of Keap1 in Tg mice may limit the ability of Nrf2 to translocate to the nucleus thereby limiting the antioxidant response and contributing to increased oxidative liver injury.
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