Cellular IAP1 regulates TRAIL-induced apoptosis in human fetal cortical neural progenitor cells

✍ Scribed by Hui Peng; Yunlong Huang; Zhiyuan Duan; Nathan Erdmann; Dongsheng Xu; Shelley Herek; Jialin Zheng

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 422 KB
• Volume: 82
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20629

✦ Synopsis

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.