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Protection of mitochondrial perturbation by human T-lymphotropic virus type 1 tax through induction of Bcl-xL expression.
- Source :
-
The Journal of laboratory and clinical medicine [J Lab Clin Med] 2003 Nov; Vol. 142 (5), pp. 341-7. - Publication Year :
- 2003
-
Abstract
- This study was designed to determine the inhibitory role of human T-lymphotropic virus type 1 (HTLV-1) tax against apoptotic cell death. We used JPX-9 cells, a Jurkat subclone generated by the stable introduction of a tax expression-plasmid vector, and induced tax expression in JPX-9 cells with CdCl2. Expression of Bcl-2, Bcl-xL, and Bax in JPX-9 cells was assessed with Western blot analysis. Both tax-negative and tax-positive JPX-9 cells were incubated in the presence of several apoptogenic stimuli, and sensitivity to apoptogenic stimuli was also evaluated. Compared with tax-negative JPX-9 cells, Bcl-xL expression was clearly augmented in tax-positive JPX-9 cells. These cells were resistant to both receptor-mediated apoptosis (induced by anti-Fas IgM and tumor necrosis factor-related apoptosis-inducing ligand) and chemical-induced apoptosis (induced by pyrrolidine dithiocarbamate, etoposide, and staurosporine), as evidenced by the presence of hypodiploid DNA-positive cells, activation of caspase-3 and caspase-9, disruption of mitochondrial transmembrane potential (DeltaPsim) and inhibition of cytochrome c release in tax-positive JPX-9 cells compared with tax-negative JPX-9 cells. Our results suggest that tax-mediated Bcl-xL expression inhibits apoptosis of activated T-cells in HTLV-1-seropositive subjects, which consequently promotes the onset of autoimmune disorders such as Sjögren's syndrome.
- Subjects :
- Antineoplastic Agents pharmacology
Apoptosis drug effects
Apoptosis physiology
Gene Expression immunology
HTLV-I Infections metabolism
Humans
Jurkat Cells
Proline pharmacology
T-Lymphocytes cytology
T-Lymphocytes physiology
Thiocarbamates pharmacology
Transfection
bcl-X Protein
HTLV-I Infections physiopathology
Human T-lymphotropic virus 1 physiology
Mitochondria metabolism
Proline analogs & derivatives
Proto-Oncogene Proteins c-bcl-2 genetics
T-Lymphocytes virology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2143
- Volume :
- 142
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of laboratory and clinical medicine
- Publication Type :
- Academic Journal
- Accession number :
- 14647038
- Full Text :
- https://doi.org/10.1016/S0022-2143(03)00134-3