日本語フィールド
著者：Chowdhry, Sudhir; Nazmy, Maiiada H.; Meakin, Paul J.; Dinkova-Kostova, Albena T.; Dinkova-Kostova, Albena T.; Walsh, Shaun V.; Tsujita, Tadayuki; Dillon, John F.; Ashford, Michael L J; Hayes, John D.題名：Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis発表情報：Free Radical Biology and Medicine 巻: 48 号: 2 ページ: 357-371キーワード：概要：Nonalcoholic steatohepatitis (NASH) arises from nonalcoholic fatty liver disease (NAFLD) as a consequence of oxidative stress. Herein we report that the development of NASH is greatly accelerated in mice lacking transcription factor Nrf2 when they are challenged with a methionine- and choline-deficient (MCD) diet. After 14 days of feeding on an MCD diet, livers from Nrf2-/- mice showed a substantial increase in macro- and microvesicular steatosis and a massive increase in the number of neutrophil polymorphs, compared to livers from wild-type mice treated similarly. Livers of Nrf2-/- mice on the MCD diet suffered more oxidative stress than their wild-type counterparts as assessed by a significant depletion of reduced glutathione that was coupled with increases in oxidized glutathione and malondialdehyde. Furthermore, livers from Nrf2-/- mice on the MCD diet suffered heightened inflammation as judged by an ∼10-fold increase in the amount of nuclear NF-κB p65 protein and ∼5-fold increases in the levels of mRNA for interleukin-1β, tumor necrosis factor α, cyclooxygenase 2, and inducible nitric oxide synthase compared with livers from similarly treated wild-type mice. Thus, impairment of Nrf2 activity may represent a major risk factor for the evolution of NAFLD to NASH. © 2009 Elsevier Inc. All rights reserved.抄録：英語フィールド
Author：Chowdhry, Sudhir; Nazmy, Maiiada H.; Meakin, Paul J.; Dinkova-Kostova, Albena T.; Dinkova-Kostova, Albena T.; Walsh, Shaun V.; Tsujita, Tadayuki; Dillon, John F.; Ashford, Michael L J; Hayes, John D.Title：Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitisAnnouncement information:Free Radical Biology and Medicine Vol: 48 Issue: 2 Page: 357-371An abstract：Nonalcoholic steatohepatitis (NASH) arises from nonalcoholic fatty liver disease (NAFLD) as a consequence of oxidative stress. Herein we report that the development of NASH is greatly accelerated in mice lacking transcription factor Nrf2 when they are challenged with a methionine- and choline-deficient (MCD) diet. After 14 days of feeding on an MCD diet, livers from Nrf2-/- mice showed a substantial increase in macro- and microvesicular steatosis and a massive increase in the number of neutrophil polymorphs, compared to livers from wild-type mice treated similarly. Livers of Nrf2-/- mice on the MCD diet suffered more oxidative stress than their wild-type counterparts as assessed by a significant depletion of reduced glutathione that was coupled with increases in oxidized glutathione and malondialdehyde. Furthermore, livers from Nrf2-/- mice on the MCD diet suffered heightened inflammation as judged by an ∼10-fold increase in the amount of nuclear NF-κB p65 protein and ∼5-fold increases in the levels of mRNA for interleukin-1β, tumor necrosis factor α, cyclooxygenase 2, and inducible nitric oxide synthase compared with livers from similarly treated wild-type mice. Thus, impairment of Nrf2 activity may represent a major risk factor for the evolution of NAFLD to NASH. © 2009 Elsevier Inc. All rights reserved.