Noxa is necessary for hydrogen peroxide-induced caspase-dependent cell death

Edited by Vladimir Skulachev

Received 24 October 2009; received in revised form 29 December 2009; accepted 11 January 2010. published online 18 January 2010.

Abstract

Oxidative stress induces apoptosis or necrosis of many cell types, which can cause tissue injury. Hydrogen peroxide (H2O2) 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 H2O2-induced apoptosis was mediated by the mitochondrial pathway in Jurkat cells. Treatment with H2O2 caused an increase of Noxa protein, via activating transcription factor 4-dependent accumulation of Noxa mRNA and inhibition of Noxa protein degradation. H2O2-induced apoptosis was strongly suppressed by silencing of Noxa, indicating that Noxa plays a crucial role in this form of apoptosis.

Structured summary

MINT-7543162: Mcl-1 (uniprotkb:Q07820) physically interacts (MI:0914) with Bim EL (uniprotkb:O43521), Bim L (uniprotkb:O43521) and NOXA (uniprotkb:Q13794) by anti bait coimmunoprecipitation (MI:0006)

Abbreviations: RT-PCR, reverse transcription polymerase chain reaction, GAPDH, glyceraldehyde-3-phosphate dehydrogenase, CRE, cAMP response element, ATF, activating transcription factor, CREB, cAMP response element-binding protein

Keywords: Hydrogen peroxide, Apoptosis, Bcl-2, Noxa, cAMP response element, Activating transcription factor 4

a Laboratory of Molecular Genetics, Department of Medical Genetics, Osaka University Medical School, Japan

b Department of Molecular Oncology, Institute of Gerontology, Nippon Medical School, Japan

Corresponding author. Address: 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Fax: +81 6 6879 3369.

PII: S0014-5793(10)00048-7

doi:10.1016/j.febslet.2010.01.026

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