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  • Title: Protection of mitochondrial perturbation by human T-lymphotropic virus type 1 tax through induction of Bcl-xL expression.
    Author: Nakashima K, Kawakami A, Hida A, Yamasaki S, Nakamura H, Kamachi M, Miyashita T, Tanaka F, Izumi Y, Tamai M, Ida H, Furuyama M, Koji T, Nakamura T, Migita K, Origuchi T, Eguchi K.
    Journal: J Lab Clin Med; 2003 Nov; 142(5):341-7. PubMed ID: 14647038.
    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.
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