Up-regulation of NAD(P)H quinone oxidoreductase 1 during human liver injury

• 作 者: Lauren M Aleksunes José EManautou Michael Goedken
• 机 构: University of Connecticut Department of Pharmaceutical Sciences,Unit 3092,Storrs,CT,United States,Un
• 出 处: World Journal of Gastroenterology
• 发表日期: 2006年12期
• 关键词: oxidoreductase quinone cirrhosis markedly staining progression nodules Minnesota

AIM:To investigate the expression and activity ofNAD(P)H quinone oxidoreductase 1(NQO1)in humanliver specimens obtained from patients with liver damagedue to acetaminophen(APAP)overdose or primarybiliary cirrhosis(PBC).METHODS:NQO1 activity was determined in cytosolfrom normal,APAP and PBC liver specimens.Westernblot and immunohistochemical staining were used todetermine patterns of NQO1 expression using a specificantibody against NQO1.RESULTS:NQO1 protein was very low in normal humanlivers.In both APAP and PBC livers,there was stronginduction of NQO1 protein levels on Western blot.Correspondingly,significant up-regulation of enzymeactivity(16-and 22-fold,P<0.05)was also observed inAPAP and PBC livers,respectively.Immunohistochemicalanalysis highlighted injury-specific patterns of NQO1staining in both APAP and PBC livers.CONCLUSION:These data demonstrate that NQO1protein and activity are markedly induced in humanlivers during both APAP overdose and PBC.Up-regulationof this cytoprotective enzyme may represent an adaptivestress response tO limit further disease progression bydetoxifying reactive species.

AIM: To investigate the expression and activity of NAD (P) H quinone oxidoreductase 1 (NQO1) in humanliver specimens obtained from patients with liver damagedue to acetaminophen (APAP) overdose or primarybiliary cirrhosis (PBC) .METHODS: NQO1 activity was determined in cytosolfrom normal , APAP and PBC liver specimens. Western blot and immunohistochemical staining were used to identify patterns of NQO1 expression using a specific antibody against NQO1.RESULTS: NQO1 protein was very low in normal humanivers. Both both APAP and PBC livers, there was strong induction of NQO1 protein levels on Significant up-regulation of enzyme activity (16-and 22-fold, P <0.05) was also observed in APAP and PBC livers, respectively. Immunohistochemicalanalysis highlighted injury-specific patterns of NQOl staging in both APAP and PBC livers. CONCLUSION: These data demonstrate that NQO1 protein and activity are markedly induced in human subjects during both APAP overdose and PBC. Up-regulation of this cytoprotecti ve enzyme may represent an adaptive response tO limit further disease progression bydetoxifying reactive species.