p53-dependent stimulation of redox-related genes in the lymphoid organs of γ-irradiated mice--identification of Haeme-oxygenase 1 as a direct p53 target gene
Recent data showed that p53 stimulates the expression of genes encoding not only pro- but also antioxidant enzymes. It was suggested that antioxidant genes could be induced under physiologic levels of stress while the prooxidant ones respond to higher level of stress. Results presented in this artic...
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| Veröffentlicht in: | Nucleic acids research 2007-11, Vol.35 (20), p.6924-6934 |
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| creator | Meiller, Anne Alvarez, Sandra Drané, Pascal Lallemand, Christophe Blanchard, Brigitte Tovey, Micheal May, Evelyne |
| description | Recent data showed that p53 stimulates the expression of genes encoding not only pro- but also antioxidant enzymes. It was suggested that antioxidant genes could be induced under physiologic levels of stress while the prooxidant ones respond to higher level of stress. Results presented in this article illustrate an additional degree of complexity. We show that the expression of Haeme-oxygenase 1 (HO-1), a stress-inducible gene that codes for an enzyme having antioxidant properties, is stimulated in a p53-dependent manner in the thymus and spleen of irradiated mice. We prove that HO-1 is a direct p53 target gene by showing that the p53RE identified within human and mouse genes is specifically bound by p53. The threshold of irradiation dose required to induce a significant response of HO-1 in the lymphoid organs of the irradiated mice is higher than that for Waf1/p21 that encodes an universal inhibitor of cell cycle. Moreover, induction of HO-1 occurs later than that of Waf1/p21. Finally, the higher stimulation of HO-1 is reached when Waf1/p21 stimulation starts to decrease. |
| doi_str_mv | 10.1093/nar/gkm824 |
| format | Article |
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It was suggested that antioxidant genes could be induced under physiologic levels of stress while the prooxidant ones respond to higher level of stress. Results presented in this article illustrate an additional degree of complexity. We show that the expression of Haeme-oxygenase 1 (HO-1), a stress-inducible gene that codes for an enzyme having antioxidant properties, is stimulated in a p53-dependent manner in the thymus and spleen of irradiated mice. We prove that HO-1 is a direct p53 target gene by showing that the p53RE identified within human and mouse genes is specifically bound by p53. The threshold of irradiation dose required to induce a significant response of HO-1 in the lymphoid organs of the irradiated mice is higher than that for Waf1/p21 that encodes an universal inhibitor of cell cycle. Moreover, induction of HO-1 occurs later than that of Waf1/p21. 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It was suggested that antioxidant genes could be induced under physiologic levels of stress while the prooxidant ones respond to higher level of stress. Results presented in this article illustrate an additional degree of complexity. We show that the expression of Haeme-oxygenase 1 (HO-1), a stress-inducible gene that codes for an enzyme having antioxidant properties, is stimulated in a p53-dependent manner in the thymus and spleen of irradiated mice. We prove that HO-1 is a direct p53 target gene by showing that the p53RE identified within human and mouse genes is specifically bound by p53. The threshold of irradiation dose required to induce a significant response of HO-1 in the lymphoid organs of the irradiated mice is higher than that for Waf1/p21 that encodes an universal inhibitor of cell cycle. Moreover, induction of HO-1 occurs later than that of Waf1/p21. Finally, the higher stimulation of HO-1 is reached when Waf1/p21 stimulation starts to decrease.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Cell Line</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Gamma Rays</subject><subject>Gene Expression Regulation, Enzymologic - radiation effects</subject><subject>Heme Oxygenase-1 - genetics</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Biology</subject><subject>Molecular Sequence Data</subject><subject>Rats</subject><subject>Sequence Homology, Nucleic Acid</subject><subject>Spleen - metabolism</subject><subject>Spleen - radiation effects</subject><subject>Thymus Gland - metabolism</subject><subject>Thymus Gland - radiation effects</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAUhSMEotPChgcAb6jEwvT6J_Fkg1RVlAFGQoKiIjaW49xkTJM42Jlq5mV4Cd6DZyLTlOFngzeW7v18zpF8kuQRg-cMcnHSmXBSX7VzLu8kMyYyTmWe8bvJDASklIGcHySHMX4BYJKl8n5ywFQuhFIwS771qaAl9tiV2A0kDq5dN2ZwviO-IgFLv6EBxwmWpMYOI3EdGVZImm3br7wriQ-16eKO_vGduhBM6W7o1lmk1O1kXeXsXnNhsEXqN9tRzkQkjJhIDCldQDuQMQ4ZTKhxuLF7kNyrTBPx4e19lFycv7w4W9Dlu1evz06XtJKcDbTIIDNgBS-QFyqrbFpmVSYLwdJSKGkZCsyVKGTJFAdjsSoMU5ZZo_gcUnGUvJhk-3XRYmnHzME0ug-uNWGrvXH6703nVrr215ozlQrgo8CzSWD1z7PF6VLvZgCCAXB2zUb2-NYs-K9rjINuXbTYNKZDv446ywFyzv8Psnw8LN-5P_4z_j7Ar28egacT4Nf97y3oXX30WB891Wfk6MS5OOBmT5pwpTMlVKoXnz7rN_n55dtLeK-XI_9k4ivjtamDi_rjBw5MAMyFzKQUPwGfc9GB</recordid><startdate>20071101</startdate><enddate>20071101</enddate><creator>Meiller, Anne</creator><creator>Alvarez, Sandra</creator><creator>Drané, Pascal</creator><creator>Lallemand, Christophe</creator><creator>Blanchard, Brigitte</creator><creator>Tovey, Micheal</creator><creator>May, Evelyne</creator><general>Oxford University Press</general><scope>FBQ</scope><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>5PM</scope></search><sort><creationdate>20071101</creationdate><title>p53-dependent stimulation of redox-related genes in the lymphoid organs of γ-irradiated mice--identification of Haeme-oxygenase 1 as a direct p53 target gene</title><author>Meiller, Anne ; 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| ispartof | Nucleic acids research, 2007-11, Vol.35 (20), p.6924-6934 |
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| subjects | Animals Base Sequence Cell Line Dose-Response Relationship, Radiation Gamma Rays Gene Expression Regulation, Enzymologic - radiation effects Heme Oxygenase-1 - genetics Heme Oxygenase-1 - metabolism Humans Kinetics Mice Mice, Inbred C57BL Molecular Biology Molecular Sequence Data Rats Sequence Homology, Nucleic Acid Spleen - metabolism Spleen - radiation effects Thymus Gland - metabolism Thymus Gland - radiation effects Tumor Suppressor Protein p53 - metabolism |
| title | p53-dependent stimulation of redox-related genes in the lymphoid organs of γ-irradiated mice--identification of Haeme-oxygenase 1 as a direct p53 target gene |
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