9 233

Cited 0 times in

Resistance of mitochondrial DNA-deficient cells to TRAIL: role of Bax in TRAIL-induced apoptosis

Authors
 Ja-Young Kim  ;  Yun-Hee Kim  ;  Inik Chang  ;  Sunshin Kim  ;  Youngmi Kim Pak  ;  Byung-Ha Oh  ;  Hideo Yagita  ;  Yong Keun Jung  ;  Young Joon Oh  ;  Myung-Shik Lee 
Citation
 Oncogene, Vol.21(20) : 3139-3148, 2002 
Journal Title
 Oncogene 
ISSN
 0950-9232 
Issue Date
2002
MeSH
Adenosine Triphosphate/physiology ; Apoptosis/drug effects ; Apoptosis/physiology* ; Apoptosis Regulatory Proteins ; BH3 Interacting Domain Death Agonist Protein ; Carcinoma, Hepatocellular/pathology ; Carrier Proteins/metabolism ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Caspases/biosynthesis ; Caspases/metabolism ; Cysteine Proteinase Inhibitors/pharmacology ; Cytochrome c Group/metabolism ; DNA, Mitochondrial/drug effects ; DNA, Mitochondrial/physiology* ; Enzyme Induction ; Ethidium/pharmacology ; Humans ; Intracellular Membranes/ultrastructure ; Liver Neoplasms/pathology ; Membrane Glycoproteins/antagonists & inhibitors ; Membrane Glycoproteins/pharmacology* ; Membrane Glycoproteins/physiology ; Membrane Potentials ; Mitochondria/physiology ; Mitochondria/ultrastructure ; Protein Transport ; Proto-Oncogene Proteins/physiology* ; Proto-Oncogene Proteins c-bcl-2* ; TNF-Related Apoptosis-Inducing Ligand ; Tumor Cells, Cultured/drug effects ; Tumor Cells, Cultured/metabolism ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/pharmacology* ; Tumor Necrosis Factor-alpha/physiology ; bcl-2-Associated X Protein
Keywords
mitochondria ; apoptosis ; TRAIL ; cytochrome c ; Bax
Abstract
Mitochondrion is one of the master players in both apoptosis and necrosis. We studied the role of mitochondrial function in TRAIL-induced apoptosis. TRAIL killed SK-Hep1 cells with characteristic features of apoptosis such as DNA fragmentation, sub-G1 ploidy peak and cytochrome c translocation. In contrast, mitochondrial DNA-deficient SK-Hep1 rho(0) cells were resistant to TRAIL. Dissipation of mitochondrial potential or cytochrome c translocation did not occur in rho(0) cells after TRAIL treatment. TRAIL induced translocation of Bax subsequent to the cleavage of Bid in parental cells. However, Bax translocation was absent in rho(0) cells, accounting for the failure of cytochrome c release in rho(0) cells. Forced expression of Bax induced caspase-3 activity in rho(0) cells. Incubation of rho(0) cells with ADP+Pi to increase intracellular ATP restored sensitivity to TRAIL. Despite different sensitivity to TRAIL, parental cells and rho(0) cells did not show significant difference in susceptibility to agonistic anti-Fas antibody, TNF-alpha or staurosporine. Our results indicate that TRAIL-induced apoptosis is dependent on intact mitochondrial function and susceptibility of mitochondrial DNA-deficient cells to apoptosis depends on the type of apoptotic stimuli. Tumor cells with mitochondrial mutations or dysfunction might have the ability to evade tumor surveillance imposed by TRAIL in vivo.
Full Text
http://www.nature.com/onc/journal/v21/n20/full/1205406a.html
DOI
10.1038/sj/onc/1205406
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Chang, In Ik(장인익)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/144796
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse