Noxa is necessary for hydrogen peroxide-induced caspase-dependent cell death.
Oxidative stress induces apoptosis or necrosis of many cell types, which can cause tissue injury. Hydrogen peroxide (H(2)O(2)) induced apoptotic death of Jurkat cells. This effect was inhibited by overexpression of human Bcl-2, by silencing of cytochrome c, and by ablation of Bax/Bak, indicating that H(2)O(2)-induced apoptosis was mediated by the mitochondrial pathway in Jurkat cells. Treatment with H(2)O(2) caused an increase of Noxa protein, via activating transcription factor 4-dependent accumulation of Noxa mRNA and inhibition of Noxa protein degradation. H(2)O(2)-induced apoptosis was strongly suppressed by silencing of Noxa, indicating that Noxa plays a crucial role in this form of apoptosis.
Aikawa
Tomonori
T
Department of Medical Genetics, Osaka University Medical School, Osaka, Japan.
Shinzawa
Koei
K
Tanaka
Nobuyuki
N
Tsujimoto
Yoshihide
Y
D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000187:drug effects; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D016877:Oxidants; C498702:PMAIP1 protein, human; D061988:Proteasome Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D051701:Activating Transcription Factor 4; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D008156:Luciferases; D020169:Caspases; D046988:Proteasome Endopeptidase Complex