Abstract
We exploited Jurkat leukemia T cell clone E6-1 as a model of Trichostatin A (TSA) effect on cellular levels of ZAP-70, LAT and SLP-76 molecules involved in the signal transduction pathway from T cell receptor to nucleus. Using reverse transcription real-time quantitative PCR and Western blotting analysis we observed that TSA resulted in ZAP-70, LAT and SLP-76 transcript and protein down-regulation in Jurkat leukemia T cells. We also found that TSA reduced half-life of ZAP-70, LAT and SLP-76 mRNAs from 4.8, 3.5, and 4.8 to approximately 2.3, 1.9 and 1.7 h, respectively. Employing the protein biosynthesis inhibitor cycloheximide, we demonstrated the involvement of RNase and/or mRNA stabilization protein in ZAP-70, LAT and SLP-76 mRNAs stabilization. The effect of TSA on ZAP-70, LAT and SLP-76 content in T cells confirms an immunosuppressive effect by TSA, and the usefulness of this histone deacetylase inhibitor in the treatment of autoimmune diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Antifungal Agents / pharmacology*
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Cell Survival / drug effects
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Down-Regulation
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Enzyme Inhibitors / pharmacology*
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Histone Deacetylase Inhibitors
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Humans
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Hydroxamic Acids / pharmacology*
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Immunosuppressive Agents / pharmacology*
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Jurkat Cells
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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RNA, Messenger / metabolism
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T-Lymphocytes / drug effects*
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T-Lymphocytes / metabolism
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ZAP-70 Protein-Tyrosine Kinase / genetics
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ZAP-70 Protein-Tyrosine Kinase / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Antifungal Agents
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Immunosuppressive Agents
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LAT protein, human
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Membrane Proteins
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Phosphoproteins
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RNA, Messenger
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SLP-76 signal Transducing adaptor proteins
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trichostatin A
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human