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J Cell Physiol ; 203(3): 547-56, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15573381

ABSTRACT

In this study, we showed the existence of a positive correlation between the amount of human immunodeficiency virus-type 1 (HIV-1) RNA in HIV-1 seropositive subjects and the plasma levels of TRAIL. Since it has been previously demonstrated that HIV-1 Tat protein up-regulates the expression of TRAIL in monocytic cells whereas tat-expressing lymphoid cells are more resistant to TRAIL cytotoxicity, we next investigated the effect of Tat on the expression/activity of both apical caspase-8 and -10, which play a key role in mediating the initial phases of apoptosis by TRAIL, and c-FLIP. Jurkat lymphoblastoid human T cell lines stably transfected with a plasmid expressing wild-type (HIV-1) tat gene showed normal levels of caspase-8 but significantly decreased levels of caspase-10 at both mRNA and protein levels with respect to Jurkat transfected with the control plasmid or with a mutated (cys22) non-functional tat cDNA. A significant decrease of caspase-10 expression/activity was also observed in transient transfection experiments with plasmid carrying tat cDNA. Moreover, c-FLIP(L) and c-FLIP(S) isoforms were up-regulated in tat-expressing cells at both mRNA and protein level in comparison with control cells. Taken together, these results provide a molecular basis to explain the resistance of tat-expressing Jurkat cells to apoptosis induced by TRAIL and, possibly, to other death-inducing ligands.


Subject(s)
CD4-Positive T-Lymphocytes/metabolism , Caspases/metabolism , Gene Products, tat/metabolism , HIV Infections/blood , HIV-1/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Glycoproteins/blood , Antibody-Dependent Cell Cytotoxicity/genetics , Apoptosis/genetics , Apoptosis Regulatory Proteins , CASP8 and FADD-Like Apoptosis Regulating Protein , CD4-Positive T-Lymphocytes/drug effects , Caspase 10 , Caspase 8 , Caspases/drug effects , Caspases/genetics , Cell Survival/genetics , DNA, Complementary/genetics , Down-Regulation/genetics , Gene Products, tat/genetics , Gene Products, tat/pharmacology , HIV Infections/genetics , HIV-1/genetics , Humans , Intracellular Signaling Peptides and Proteins/drug effects , Jurkat Cells , Membrane Glycoproteins/toxicity , Mutation/genetics , RNA, Messenger/metabolism , RNA, Viral/genetics , RNA, Viral/metabolism , TNF-Related Apoptosis-Inducing Ligand , Tumor Necrosis Factor-alpha/toxicity , Up-Regulation/genetics , tat Gene Products, Human Immunodeficiency Virus
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