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

Hui Peng, Yunlong Huang, Zhiyuan Duan, Nathan Erdmann, Dongsheng Xu, Shelley Herek, Jialin Zheng

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)295-305
Number of pages11
JournalJournal of Neuroscience Research
Volume82
Issue number3
DOIs
StatePublished - Nov 1 2005

Keywords

  • Apoptosis
  • Human neural progenitor cell (NPC)
  • TRAIL
  • c-IAP1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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