c-Jun/AP-1, but not NF-kappa B, is a mediator for oxidant-initiated apoptosis in glomerular mesangial cells.
Oxidant stress is a trigger of cell death in various cell types. Hydrogen peroxide (H2O2) induced mesangial cell death with nuclear condensation and DNA fragmentation typical of apoptosis. To explore molecular mechanisms involved in this process, redox-sensitive transacting molecules, activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B), have been brought into focus. Northern blot analysis and transient transfection assays using reporter plasmids showed that H2O2 activated both AP-1 and NF-kappa B. Downregulation of c-Jun/AP-1 using a transdominant negative mutant of c-jun, an antisense c-jun, or a pharmacologic inhibitor curcumin inhibited the H2O2-initiated apoptosis. In contrast, inhibition of the NF-kappa B activation using a transdominant negative mutant of the p50 NF-kappa B subunit did not affect the H2O2-triggered cellular death. These data elucidated that c-Jun/AP-1, but not NF-kappa B, is involved in the oxidant-initiated cell death program in glomerular mesangial cells.
Ishikawa
Y
Y
Department of Medicine, University College London Medical School, United Kingdom.
Yokoo
T
T
Kitamura
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002999:Clone Cells; D016758:Genes, jun; D005822:Genetic Vectors; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006678:HIV / Q000235:genetics; D016325:HIV Long Terminal Repeat; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009154:Mutation; D016328:NF-kappa B / Q000096:biosynthesis*; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*; D014162:Transfection; D001616:beta-Galactosidase / Q000096:biosynthesis
D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D006861:Hydrogen Peroxide; D001616:beta-Galactosidase