Over-expression of JunB inhibits mitochondrial stress and cytotoxicity in human lymphoma cells exposed to chronic oxidative stress.
Activator protein-1 can induce either cell survival or death, which is controlled by opposing effects of different Jun members. It is generally accepted that c-Jun is pro-apoptotic, but that JunD is anti-apoptotic in stress-exposed cells. Additionally, although there are reports suggesting that JunB plays a protective role, its role in stress-induced apoptosis remains unclear. Here, we investigated the role of JunB in H(2)O(2)-induced cell death using cells that over-expressed the protein or were transfected with si-JunB. Inhibition of JunB expression accelerated H(2)O(2)-mediated loss of mitochondrial membrane potential (MMP) and cytotoxicity. Conversely, over-expression of JunB protein led to significant inhibition of the MMP loss and cell death. The increase in JunB expression also attenuated nuclear relocation of apoptosis-inducing factor and mitochondrial Bcl-2 reduction that occurred following H(2)O(2) exposure. These results suggest that JunB can signal survival against oxidant-mediated cell death by suppressing mitochondrial stress. [BMB reports 2010; 43(1): 57-61].
Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536-0001, USA.
Young-Ok
YO
Son
Jung-Sun
JS
Heo
Tae-Geum
TG
Kim
Young-Mi
YM
Jeon
Jong-Ghee
JG
Kim
Jeong-Chae
JC
Lee
D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019169:Jurkat Cells; D008223:Lymphoma / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
D051033:Apoptosis Inducing Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D006861:Hydrogen Peroxide