Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia
TRB3 (tribbles 3), an apoptosis-regulated gene, increases during endoplasmic reticulum stress. Hypoxia can induce inflammatory mediators and apoptosis in cardiomyocytes. However, the expression of TRB3 in cardiomyocyte apoptosis under hypoxia is not thoroughly known. We investigated the regulation m...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-05-01
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| Series: | Journal of the Formosan Medical Association |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0929664616301784 |
| _version_ | 1818234578639257600 |
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| author | Wen-Pin Cheng Huey-Ming Lo Bao-Wei Wang Su-Kiat Chua Ming-Jen Lu Kou-Gi Shyu |
| author_facet | Wen-Pin Cheng Huey-Ming Lo Bao-Wei Wang Su-Kiat Chua Ming-Jen Lu Kou-Gi Shyu |
| author_sort | Wen-Pin Cheng |
| collection | DOAJ |
| description | TRB3 (tribbles 3), an apoptosis-regulated gene, increases during endoplasmic reticulum stress. Hypoxia can induce inflammatory mediators and apoptosis in cardiomyocytes. However, the expression of TRB3 in cardiomyocyte apoptosis under hypoxia is not thoroughly known. We investigated the regulation mechanism of TRB3 expression and apoptosis induced by hypoxia in cardiomyocytes.
Methods: An in vivo model of acute myocardial infarction (AMI) was applied in adult Wistar rats to induce myocardial hypoxia. Rat neonatal cardiomyocytes were subjected to 2.5% O2 to induce hypoxia.
Results: The expression of TRB3 was evaluated in cultured rat neonatal cardiomyocytes subjected to hypoxia. Hypoxia significantly enhanced TRB3 protein and mRNA expression. Adding c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA), tumor necrosis factor-α (TNF-α) antibody, and atorvastatin 30 minutes before hypoxia reversed the induction of TRB3 protein. A gel-shift assay showed the DNA-binding activity of growth arrest and DNA damage-inducible gene 153 (GADD153), which increased after hypoxia. Hypoxia increased, whereas the TRB3-mut plasmid, SP600125, and TNF-α antibody abolished the hypoxia-induced TRB3 promoter activity. Hypoxia increased the secretion of TNF-α from cardiomyocytes. Exogenous administration of TNF-α recombinant protein to the cardiomyocytes without hypoxia increased TRB3 protein expression, similar to that observed after hypoxia. Hypoxia-induced cardiomyocyte apoptosis is inhibited by TRB3 siRNA, the TNF-α antibody, and atorvastatin. Atorvastatin reduced the TRB3 expression and cardiomyocyte apoptosis induced by AMI. Hypoxia induces TRB3 through TNF-α, JNK, and the GADD153 pathway.
Conclusion: Treatment of atorvastatin inhibits the expression of TRB3 and cardiomyocyte apoptosis induced by AMI and hypoxia. |
| first_indexed | 2024-12-12T11:40:18Z |
| format | Article |
| id | doaj.art-723cf620dd1a4e2d8e5397c2cb8f7246 |
| institution | Directory Open Access Journal |
| issn | 0929-6646 |
| language | English |
| last_indexed | 2024-12-12T11:40:18Z |
| publishDate | 2017-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of the Formosan Medical Association |
| spelling | doaj.art-723cf620dd1a4e2d8e5397c2cb8f72462022-12-22T00:25:33ZengElsevierJournal of the Formosan Medical Association0929-66462017-05-01116538839710.1016/j.jfma.2016.07.010Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxiaWen-Pin Cheng0Huey-Ming Lo1Bao-Wei Wang2Su-Kiat Chua3Ming-Jen Lu4Kou-Gi Shyu5Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, TaiwanDivision of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, TaiwanDepartment of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, TaiwanDivision of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, TaiwanDivision of Cardiovascular Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, TaiwanDivision of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, TaiwanTRB3 (tribbles 3), an apoptosis-regulated gene, increases during endoplasmic reticulum stress. Hypoxia can induce inflammatory mediators and apoptosis in cardiomyocytes. However, the expression of TRB3 in cardiomyocyte apoptosis under hypoxia is not thoroughly known. We investigated the regulation mechanism of TRB3 expression and apoptosis induced by hypoxia in cardiomyocytes. Methods: An in vivo model of acute myocardial infarction (AMI) was applied in adult Wistar rats to induce myocardial hypoxia. Rat neonatal cardiomyocytes were subjected to 2.5% O2 to induce hypoxia. Results: The expression of TRB3 was evaluated in cultured rat neonatal cardiomyocytes subjected to hypoxia. Hypoxia significantly enhanced TRB3 protein and mRNA expression. Adding c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA), tumor necrosis factor-α (TNF-α) antibody, and atorvastatin 30 minutes before hypoxia reversed the induction of TRB3 protein. A gel-shift assay showed the DNA-binding activity of growth arrest and DNA damage-inducible gene 153 (GADD153), which increased after hypoxia. Hypoxia increased, whereas the TRB3-mut plasmid, SP600125, and TNF-α antibody abolished the hypoxia-induced TRB3 promoter activity. Hypoxia increased the secretion of TNF-α from cardiomyocytes. Exogenous administration of TNF-α recombinant protein to the cardiomyocytes without hypoxia increased TRB3 protein expression, similar to that observed after hypoxia. Hypoxia-induced cardiomyocyte apoptosis is inhibited by TRB3 siRNA, the TNF-α antibody, and atorvastatin. Atorvastatin reduced the TRB3 expression and cardiomyocyte apoptosis induced by AMI. Hypoxia induces TRB3 through TNF-α, JNK, and the GADD153 pathway. Conclusion: Treatment of atorvastatin inhibits the expression of TRB3 and cardiomyocyte apoptosis induced by AMI and hypoxia.http://www.sciencedirect.com/science/article/pii/S0929664616301784AMIatorvastatincardiomyocyteshypoxiaTRB3 |
| spellingShingle | Wen-Pin Cheng Huey-Ming Lo Bao-Wei Wang Su-Kiat Chua Ming-Jen Lu Kou-Gi Shyu Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia Journal of the Formosan Medical Association AMI atorvastatin cardiomyocytes hypoxia TRB3 |
| title | Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia |
| title_full | Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia |
| title_fullStr | Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia |
| title_full_unstemmed | Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia |
| title_short | Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia |
| title_sort | atorvastatin alleviates cardiomyocyte apoptosis by suppressing trb3 induced by acute myocardial infarction and hypoxia |
| topic | AMI atorvastatin cardiomyocytes hypoxia TRB3 |
| url | http://www.sciencedirect.com/science/article/pii/S0929664616301784 |
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