We previously reported that the inhibition of @entity12609 and @entity2041 peroxidase activities by treatment with @entity7083 ( @entity10664 ) and @entity58020 evoked sustained increases in the levels of reactive @entity26 species and apoptosis in @entity35 primary hepatocytes. Apoptosis was accompanied by increased expression of BimEL, following activation of extracellular signal-regulated kinase. The aim of this study was to characterize the mechanism underlying hepatocyte apoptosis by identifying the transcription factor that induces BimEL expression. The bim promoter region was cloned into a promoterless-luc vector, and promoter activity was monitored by a luciferase assay. The luciferase activity increased in the presence of @entity10664 + @entity58020 . Pretreatment with a MEK inhibitor, @entity5732 , or an antioxidant, @entity620 , suppressed the promoter activity. Furthermore, @entity10664 + @entity58020 -induced luciferase activity was attenuated by mutation of the activator protein-1 binding site in the bim promoter region. The amounts of total and phosphorylated @entity5019 increased over time in the presence of @entity10664 + @entity58020 , whereas the amounts of total and phosphorylated c-Jun remained unchanged. Chromatin immunoprecipitation revealed that both @entity5019 and c-Jun localized to the activator protein-1-binding site in the bim promoter region. BimEL expression and hepatocyte apoptosis were suppressed by knockdown of @entity5019 and c-Jun, respectively. These results indicate that increases in @entity5019 following extracellular signal-regulated kinase activation are critical for BimEL upregulation and apoptosis.

Increased expression of XXXX by extracellular signal-regulated kinase activation under sustained oxidative stress elicits BimEL upregulation and hepatocyte apoptosis.

@entity58020 :: ('MESH:C046062', 'Chemical') :: ['mercaptosuccinic acid'] @entity5732 :: ('MESH:C113580', 'Chemical') :: ['U0126'] @entity10664 :: ('CHEBI:37924', 'Chemical') :: ['ATZ'] @entity620 :: ('MESH:D001205', 'Chemical') :: ['vitamin C'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity2041 :: ('MESH:D005978', 'Chemical') :: ['glutathione'] @entity5019 :: ('314322(Tax:10116)', 'Gene') :: ['c-Fos'] @entity7083 :: ('MESH:D000640', 'Chemical') :: ['3-amino-1,2,4-triazole'] @entity12609 :: ('24248(Tax:10116)', 'Gene') :: ['catalase'] @entity35 :: ('10116', 'Species') :: ['rat']
@entity5019 :: (314322(Tax:10116),Gene) :: ['c-Fos']
