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

Academic Article

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. © 2005 Wiley-Liss, Inc.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Peng H; Huang Y; Duan Z; Erdmann N; Xu D; Herek S; Zheng J
  • Start Page

  • 295
  • End Page

  • 305
  • Volume

  • 82
  • Issue

  • 3