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Cellular IAP1 regulates TRAIL‐induced apoptosis in human fetal cortical neural progenitor cells
Author(s) -
Peng Hui,
Huang Yunlong,
Duan Zhiyuan,
Erdmann Nathan,
Xu Dongsheng,
Herek Shelley,
Zheng Jialin
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20629
Subject(s) - apoptosis , microbiology and biotechnology , neural stem cell , biology , progenitor cell , small interfering rna , inhibitor of apoptosis , caspase , programmed cell death , cancer research , stem cell , cell culture , transfection , biochemistry , genetics
Neural stem/progenitor cells (NPCs) are present in the developing and adult central nervous system. NPC apoptosis is an important aspect of normal brain development. We show that tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) receptor 2 is highly expressed on human NPCs derived from fetal cortex, yet TRAIL induces only minimal levels of apoptosis in NPCs. Caspase‐8 mRNA and protein, an important factor in the TRAIL‐mediated death pathway, is present at low levels in human NPCs. In contrast, inhibitors of apoptosis proteins (IAP), such as c‐IAP1, are highly expressed. The transcription inhibitor actinomycin D sensitized human NPCs to TRAIL‐induced apoptosis. Further, inhibition of cellular inhibitors of apoptosis protein 1 (c‐IAP1) expression by small interfering RNA (siRNA) increased TRAIL‐mediated caspase‐3 activation and apoptosis; thus, c‐IAP1 protects NPCs against TRAIL‐induced apoptosis and suppresses caspase‐3 activation. These findings illustrate the mechanisms for NPC resistance to apoptotic agonists such as TRAIL, and demonstrate a potentially important mechanism in CNS disease states. © 2005 Wiley‐Liss, Inc.