CRE-Mediated transcriptional activation is involved in cAMP protection of T-cell receptor-induced apoptosis but not in cAMP potentiation of glucocorticoid-mediated programmed cell death
Apoptosis of thymic cells induced by glucocorticoids (GC) and T-cell receptor (TCR) engagement are mutually antagonistic. We demonstrate that cAMP enhances GC and antagonizes TCR (anti-CD3) apoptosis on the same cell (DO-11.10 and 2B4.11 T-cell hybridomas). We analyzed the activity of several transc...
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todo:paper_01674889_v1542_n1-3_p139_Igaz2023-10-03T15:04:48Z CRE-Mediated transcriptional activation is involved in cAMP protection of T-cell receptor-induced apoptosis but not in cAMP potentiation of glucocorticoid-mediated programmed cell death Igaz, L.M. Refojo, D. Costas, M.A. Holsboer, F. Arzt, E. Apoptosis CAMP responsive element binding protein Cyclic AMP Glucocorticoids T cell receptor bucladesine CD3 antigen cyclic AMP cyclic AMP responsive element binding protein dexamethasone DNA glucocorticoid immunoglobulin enhancer binding protein monoclonal antibody CD3 oligomer T lymphocyte receptor animal cell apoptosis article controlled study cyclic AMP responsive element enzyme activity enzyme inhibition genetic transfection hybridoma cell culture mouse nonhuman priority journal regulatory mechanism T lymphocyte transcription initiation Animals Apoptosis Cell Line Cyclic AMP Cyclic AMP Response Element-Binding Protein Flow Cytometry Glucocorticoids Hybridomas Mice Receptors, Antigen, T-Cell Response Elements T-Lymphocytes Transcription, Genetic Transfection Apoptosis of thymic cells induced by glucocorticoids (GC) and T-cell receptor (TCR) engagement are mutually antagonistic. We demonstrate that cAMP enhances GC and antagonizes TCR (anti-CD3) apoptosis on the same cell (DO-11.10 and 2B4.11 T-cell hybridomas). We analyzed the activity of several transcription factors in this cAMP dual, stimulus-dependent, regulatory action. Anti-CD3 increases kB-activity which is inhibited by CPTcAMP or dexamethasone (DEX), supporting the proapoptotic role of NFkB on TCR-induced apoptosis. Anti-CD3 not only increases kB- but diminishes GC response element (GRE)-activity induced by DEX, suggesting that TCR-mediated blockade of GC-induced apoptosis involves not only the proposed antiapoptotic action of NF-kB on GC, but also the inhibition of GRE-regulated proapoptotic genes. To test the involvement of CRE-driven transcription in the cAMP dual apoptotic regulation, cells were transfected with a CRE decoy DNA oligomer. Blockade of CRE transactivation with decoy targeting of CRE completely blocked the protection of TCR-induced apoptosis by cAMP, while it did not modify the enhancement by cAMP on GC-induced apoptosis. We show that CRE-binding factors have a definite role in T-cell apoptosis: they are involved in cAMP protection of TCR- but not in cAMP potentiation of GC-induced apoptosis. © 2002 Elsevier Science B.V. All rights reserved. Fil:Refojo, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Costas, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01674889_v1542_n1-3_p139_Igaz |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Apoptosis CAMP responsive element binding protein Cyclic AMP Glucocorticoids T cell receptor bucladesine CD3 antigen cyclic AMP cyclic AMP responsive element binding protein dexamethasone DNA glucocorticoid immunoglobulin enhancer binding protein monoclonal antibody CD3 oligomer T lymphocyte receptor animal cell apoptosis article controlled study cyclic AMP responsive element enzyme activity enzyme inhibition genetic transfection hybridoma cell culture mouse nonhuman priority journal regulatory mechanism T lymphocyte transcription initiation Animals Apoptosis Cell Line Cyclic AMP Cyclic AMP Response Element-Binding Protein Flow Cytometry Glucocorticoids Hybridomas Mice Receptors, Antigen, T-Cell Response Elements T-Lymphocytes Transcription, Genetic Transfection |
| spellingShingle |
Apoptosis CAMP responsive element binding protein Cyclic AMP Glucocorticoids T cell receptor bucladesine CD3 antigen cyclic AMP cyclic AMP responsive element binding protein dexamethasone DNA glucocorticoid immunoglobulin enhancer binding protein monoclonal antibody CD3 oligomer T lymphocyte receptor animal cell apoptosis article controlled study cyclic AMP responsive element enzyme activity enzyme inhibition genetic transfection hybridoma cell culture mouse nonhuman priority journal regulatory mechanism T lymphocyte transcription initiation Animals Apoptosis Cell Line Cyclic AMP Cyclic AMP Response Element-Binding Protein Flow Cytometry Glucocorticoids Hybridomas Mice Receptors, Antigen, T-Cell Response Elements T-Lymphocytes Transcription, Genetic Transfection Igaz, L.M. Refojo, D. Costas, M.A. Holsboer, F. Arzt, E. CRE-Mediated transcriptional activation is involved in cAMP protection of T-cell receptor-induced apoptosis but not in cAMP potentiation of glucocorticoid-mediated programmed cell death |
| topic_facet |
Apoptosis CAMP responsive element binding protein Cyclic AMP Glucocorticoids T cell receptor bucladesine CD3 antigen cyclic AMP cyclic AMP responsive element binding protein dexamethasone DNA glucocorticoid immunoglobulin enhancer binding protein monoclonal antibody CD3 oligomer T lymphocyte receptor animal cell apoptosis article controlled study cyclic AMP responsive element enzyme activity enzyme inhibition genetic transfection hybridoma cell culture mouse nonhuman priority journal regulatory mechanism T lymphocyte transcription initiation Animals Apoptosis Cell Line Cyclic AMP Cyclic AMP Response Element-Binding Protein Flow Cytometry Glucocorticoids Hybridomas Mice Receptors, Antigen, T-Cell Response Elements T-Lymphocytes Transcription, Genetic Transfection |
| description |
Apoptosis of thymic cells induced by glucocorticoids (GC) and T-cell receptor (TCR) engagement are mutually antagonistic. We demonstrate that cAMP enhances GC and antagonizes TCR (anti-CD3) apoptosis on the same cell (DO-11.10 and 2B4.11 T-cell hybridomas). We analyzed the activity of several transcription factors in this cAMP dual, stimulus-dependent, regulatory action. Anti-CD3 increases kB-activity which is inhibited by CPTcAMP or dexamethasone (DEX), supporting the proapoptotic role of NFkB on TCR-induced apoptosis. Anti-CD3 not only increases kB- but diminishes GC response element (GRE)-activity induced by DEX, suggesting that TCR-mediated blockade of GC-induced apoptosis involves not only the proposed antiapoptotic action of NF-kB on GC, but also the inhibition of GRE-regulated proapoptotic genes. To test the involvement of CRE-driven transcription in the cAMP dual apoptotic regulation, cells were transfected with a CRE decoy DNA oligomer. Blockade of CRE transactivation with decoy targeting of CRE completely blocked the protection of TCR-induced apoptosis by cAMP, while it did not modify the enhancement by cAMP on GC-induced apoptosis. We show that CRE-binding factors have a definite role in T-cell apoptosis: they are involved in cAMP protection of TCR- but not in cAMP potentiation of GC-induced apoptosis. © 2002 Elsevier Science B.V. All rights reserved. |
| format |
JOUR |
| author |
Igaz, L.M. Refojo, D. Costas, M.A. Holsboer, F. Arzt, E. |
| author_facet |
Igaz, L.M. Refojo, D. Costas, M.A. Holsboer, F. Arzt, E. |
| author_sort |
Igaz, L.M. |
| title |
CRE-Mediated transcriptional activation is involved in cAMP protection of T-cell receptor-induced apoptosis but not in cAMP potentiation of glucocorticoid-mediated programmed cell death |
| title_short |
CRE-Mediated transcriptional activation is involved in cAMP protection of T-cell receptor-induced apoptosis but not in cAMP potentiation of glucocorticoid-mediated programmed cell death |
| title_full |
CRE-Mediated transcriptional activation is involved in cAMP protection of T-cell receptor-induced apoptosis but not in cAMP potentiation of glucocorticoid-mediated programmed cell death |
| title_fullStr |
CRE-Mediated transcriptional activation is involved in cAMP protection of T-cell receptor-induced apoptosis but not in cAMP potentiation of glucocorticoid-mediated programmed cell death |
| title_full_unstemmed |
CRE-Mediated transcriptional activation is involved in cAMP protection of T-cell receptor-induced apoptosis but not in cAMP potentiation of glucocorticoid-mediated programmed cell death |
| title_sort |
cre-mediated transcriptional activation is involved in camp protection of t-cell receptor-induced apoptosis but not in camp potentiation of glucocorticoid-mediated programmed cell death |
| url |
http://hdl.handle.net/20.500.12110/paper_01674889_v1542_n1-3_p139_Igaz |
| work_keys_str_mv |
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