GMEB1, a novel endogenous caspase inhibitor, prevents hypoxia- and oxidative stress-induced neuronal apoptosis.
The interaction of glucocorticoid modulatory element-binding protein 1 (GMEB1) with procaspase-2, -8, or -9 prevents caspase oligomerization and maturation. In the present study, we examined the effect of GMEB1 on neuronal apoptosis induced by hypoxia and oxidative stress. GMEB1 effectively attenuated caspase activation and apoptosis caused by these stresses in human neuroblastoma SK-N-MC cells, indicating that it functions as a potent inhibitor of caspase activation and apoptosis in response to oxidative stress. We propose that GMEB1 blocks pro-apoptosis signals induced by a variety of stresses.
Nakagawa
Tadashi
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Tsuruma
Kazuhiro
K
Uehara
Takashi
T
Nomura
Yasuyuki
Y
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D053143:Caspase 2 / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000378:metabolism*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism*; D016877:Oxidants / Q000037:antagonists & inhibitors / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C490664:GMEB1 protein, human; D016877:Oxidants; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D053143:Caspase 2; D020169:Caspases