TY - JOUR
T1 - Cellular IAP1 regulates TRAIL-induced apoptosis in human fetal cortical neural progenitor cells
AU - Peng, Hui
AU - Huang, Yunlong
AU - Duan, Zhiyuan
AU - Erdmann, Nathan
AU - Xu, Dongsheng
AU - Herek, Shelley
AU - Zheng, Jialin
PY - 2005/11/1
Y1 - 2005/11/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Human neural progenitor cell (NPC)
KW - TRAIL
KW - c-IAP1
UR - http://www.scopus.com/inward/record.url?scp=27644573005&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27644573005&partnerID=8YFLogxK
U2 - 10.1002/jnr.20629
DO - 10.1002/jnr.20629
M3 - Article
C2 - 16180223
AN - SCOPUS:27644573005
SN - 0360-4012
VL - 82
SP - 295
EP - 305
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 3
ER -