A novel WD-40 repeat protein WDR26 suppresses H2O2-induced cell death in neural cells.
WD-40 repeat proteins play important roles in a variety of cellular functions, such as cell growth, proliferation, apoptosis and intracellular signal transduction. We previously identified a novel member of this family, WDR26. To examine the biological function of WDR26, we used hWDR26 plasmids and antisense phosphorothioate oligodeoxynucleotides (asODNs) against WDR26 to examine its role in response to oxidative stress in human SH-SY5Y neuroblastoma cells. Our results showed that H2O2 at 0.5mM substantially induced cell death and significantly up-regulated the WDR26 expression, and WDR26 over-expression in turn strongly suppressed H2O2-induced cell death. Moreover, asODNs markedly inhibited the de novo biosynthesis of WDR26, which contributed to enhanced cell death induced by H2O2. Finally, we found that WDR26 over-expression also down-regulated the transcriptional activity of AP-1 during H2O2-induced SH-SY5Y cell death. Taken together, these results indicated that WDR26 was up-regulated by oxidative stress and played a key role in H2O2-induced SH-SY5Y cell death, which may be mediated by the down-regulation of AP-1 transcriptional activity.
Zhao
Jie
J
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China.
Liu
Ying
Y
Wei
Xing
X
Yuan
Can
C
Yuan
Xianrui
X
Xiao
Xianzhong
X
D048868:Adaptor Proteins, Signal Transducing; D000704:Analysis of Variance; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004277:DNA, Single-Stranded / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009447:Neuroblastoma; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects*
D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D004277:DNA, Single-Stranded; D016877:Oxidants; D011506:Proteins; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D018808:Transcription Factor AP-1; C543172:WDR26 protein, human; D006861:Hydrogen Peroxide; D053148:Caspase 3; C022616:thiazolyl blue