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 C Zheng

Research output: Contribution to journalArticle

23 Citations (Scopus)

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

Fingerprint

Neural Stem Cells
Stem Cells
Apoptosis
Inhibitor of Apoptosis Proteins
Caspase 3
TNF-Related Apoptosis-Inducing Ligand Receptors
Caspase 8
Central Nervous System Diseases
Dactinomycin
Small Interfering RNA
Central Nervous System
Tumor Necrosis Factor-alpha
Ligands
Messenger RNA
Brain

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Cellular IAP1 regulates TRAIL-induced apoptosis in human fetal cortical neural progenitor cells. / Peng, Hui; Huang, Yunlong; Duan, Zhiyuan; Erdmann, Nathan; Xu, Dongsheng; Herek, Shelley; Zheng, Jialin C.

In: Journal of Neuroscience Research, Vol. 82, No. 3, 01.11.2005, p. 295-305.

Research output: Contribution to journalArticle

Peng, Hui ; Huang, Yunlong ; Duan, Zhiyuan ; Erdmann, Nathan ; Xu, Dongsheng ; Herek, Shelley ; Zheng, Jialin C. / Cellular IAP1 regulates TRAIL-induced apoptosis in human fetal cortical neural progenitor cells. In: Journal of Neuroscience Research. 2005 ; Vol. 82, No. 3. pp. 295-305.
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