期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 82, 期 3, 页码 295-305出版社
WILEY
DOI: 10.1002/jnr.20629
关键词
human neural progenitor cell (NPC); apoptosis; TRAIL; c-IAP1
资金
- NCRR NIH HHS [P20 RR15635] Funding Source: Medline
- NINDS NIH HHS [P01 NS043985, R01 NS 41858] Funding Source: Medline
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. (c) 2005 Wiley-Liss, Inc.
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