Protection of mitochondrial perturbation by human T-lymphotropic virus type 1 tax through induction of Bcl-xL expression.
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.
Nakashima
Koto
K
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Kawakami
Atsushi
A
Hida
Ayumi
A
Yamasaki
Satoshi
S
Nakamura
Hideki
H
Kamachi
Makoto
M
Miyashita
Taiichiro
T
Tanaka
Fumiko
F
Izumi
Yasumori
Y
Tamai
Mami
M
Ida
Hiroaki
H
Furuyama
Masako
M
Koji
Takehiko
T
Nakamura
Tatsufumi
T
Migita
Kiyoshi
K
Origuchi
Tomoki
T
Eguchi
Katsumi
K
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000276:immunology; D015490:HTLV-I Infections / Q000378:metabolism / Q000503:physiopathology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008928:Mitochondria / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology / Q000821:virology*; D013859:Thiocarbamates / Q000494:pharmacology; D014162:Transfection; D051020:bcl-X Protein
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D013859:Thiocarbamates; D051020:bcl-X Protein; C066229:prolinedithiocarbamate; D011392:Proline