Document Detail


Preferential involvement of mitochondria in Toll-like receptor 3 agonist-induced neuroblastoma cell apoptosis, but not in inhibition of cell growth.
MedLine Citation:
PMID:  22187010     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Double-stranded RNA (dsRNA) can mediate its therapeutic effect through Toll-like receptor 3 (TLR3) expressed on tumor cells including neuroblastoma. We used synthetic dsRNA polyinosinic-polycytidylic acid [Poly(I:C)] as a TLR3 agonist to treat TLR3-expressing SK-N-AS neuroblatoma (NB) cells. We found up-regulation of endoplasmic reticulum (ER) stress proteins glucose-regulated protein 78 and inositol-requiring enzyme 1. Bafilomycin A1, an inhibitor of ER function, effectively blocked poly(I:C)-induced activation of caspase-8, -9, and -3, MnSOD and glutathione peroxidase 1 and reduced poly(I:C)-induced SK-N-AS apoptosis. Pan caspase inhibitor and inhibitor of caspase-9, but not of caspase-8, inhibited poly(I:C)-induced activated caspase-3 expression. Rho zero (ρ(0))-SK-N-AS cells were resistant to poly(I:C)-induced mitochondrial reactive oxygen species production and apoptosis, but not to inhibition of cell growth, as compared to parent SK-N-AS cells. Taking together, these findings suggest that mitochondria are preferentially involved in poly(I:C)-induced NB cell apoptosis, but not in inhibition of cell growth. A crosstalk between mitochondria and ER is implicated.
Authors:
Jiin-Haur Chuang; Tsu-Kung Lin; Ming-Hong Tai; Chia-Wei Liou; Sheng-Teng Huang; Chia-Ling Wu; Hung-Yi Lin; Pei-Wen Wang
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-21
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  -     ISSN:  1573-675X     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
The Mitochondrial Research Unit, and the Division of Pediatric Surgery, Kaohsiung Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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