p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53‐Lys118 acetylation
Abstract Myocardial infarction, an irreversible cardiac tissue damage, involves progressive loss of cardiomyocytes due to p53‐mediated apoptosis. Oxygenation is known to promote cardiac survival through activation of NOS3 gene. We hypothesized a dual role for p53, which, depending on oxygenation, ca...
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| Format: | Article |
| Language: | English |
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Springer Nature
2013-10-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.1002/emmm.201202055 |
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| author | Rajan Gogna Esha Madan Mahmood Khan Uttam Pati Periannan Kuppusamy |
| author_facet | Rajan Gogna Esha Madan Mahmood Khan Uttam Pati Periannan Kuppusamy |
| author_sort | Rajan Gogna |
| collection | DOAJ |
| description | Abstract Myocardial infarction, an irreversible cardiac tissue damage, involves progressive loss of cardiomyocytes due to p53‐mediated apoptosis. Oxygenation is known to promote cardiac survival through activation of NOS3 gene. We hypothesized a dual role for p53, which, depending on oxygenation, can elicit apoptotic death signals or NOS3‐mediated survival signals in the infarct heart. p53 exhibited a differential DNA‐binding, namely, BAX‐p53RE in the infarct heart or NOS3‐p53RE in the oxygenated heart, which was regulated by oxygen‐induced, post‐translational modification of p53. In the infarct heart, p53 was heavily acetylated at Lys118 residue, which was exclusively reversed in the oxygenated heart, apparently regulated by oxygen‐dependent expression of TIP60. The inhibition of Lys118 acetylation promoted the generation of NOS3‐promoting prosurvival form of p53. Thus, oxygenation switches p53‐DNA interaction by regulating p53 core‐domain acetylation, promoting a prosurvival transcription activity of p53. Understanding this novel oxygen‐p53 survival pathway will open new avenues in cardioprotection molecular therapy. |
| format | Article |
| id | doaj-art-6f7cd6b260d24775bd100fa0d5359890 |
| institution | OA Journals |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2013-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-6f7cd6b260d24775bd100fa0d53598902025-08-20T02:18:31ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842013-10-015111662168310.1002/emmm.201202055p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53‐Lys118 acetylationRajan Gogna0Esha Madan1Mahmood Khan2Uttam Pati3Periannan Kuppusamy4Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Ohio State University Wexner Medical CenterTranscription and Human Biology Laboratory, School of Biotechnology, Jawaharlal Nehru UniversityDorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Ohio State University Wexner Medical CenterAbstract Myocardial infarction, an irreversible cardiac tissue damage, involves progressive loss of cardiomyocytes due to p53‐mediated apoptosis. Oxygenation is known to promote cardiac survival through activation of NOS3 gene. We hypothesized a dual role for p53, which, depending on oxygenation, can elicit apoptotic death signals or NOS3‐mediated survival signals in the infarct heart. p53 exhibited a differential DNA‐binding, namely, BAX‐p53RE in the infarct heart or NOS3‐p53RE in the oxygenated heart, which was regulated by oxygen‐induced, post‐translational modification of p53. In the infarct heart, p53 was heavily acetylated at Lys118 residue, which was exclusively reversed in the oxygenated heart, apparently regulated by oxygen‐dependent expression of TIP60. The inhibition of Lys118 acetylation promoted the generation of NOS3‐promoting prosurvival form of p53. Thus, oxygenation switches p53‐DNA interaction by regulating p53 core‐domain acetylation, promoting a prosurvival transcription activity of p53. Understanding this novel oxygen‐p53 survival pathway will open new avenues in cardioprotection molecular therapy.https://doi.org/10.1002/emmm.201202055lysine acetylationmyocardial infarctionNOS3oxygenationp53 |
| spellingShingle | Rajan Gogna Esha Madan Mahmood Khan Uttam Pati Periannan Kuppusamy p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53‐Lys118 acetylation EMBO Molecular Medicine lysine acetylation myocardial infarction NOS3 oxygenation p53 |
| title | p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53‐Lys118 acetylation |
| title_full | p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53‐Lys118 acetylation |
| title_fullStr | p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53‐Lys118 acetylation |
| title_full_unstemmed | p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53‐Lys118 acetylation |
| title_short | p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53‐Lys118 acetylation |
| title_sort | p53 s choice of myocardial death or survival oxygen protects infarct myocardium by recruiting p53 on nos3 promoter through regulation of p53 lys118 acetylation |
| topic | lysine acetylation myocardial infarction NOS3 oxygenation p53 |
| url | https://doi.org/10.1002/emmm.201202055 |
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