AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia
The AKT (protein kinase B, PKB) family has been shown to participate in diverse cellular processes, including apoptosis. Previous studies demonstrated that protein kinase B2 (AKT2−/−) mice heart was sensitized to apoptosis in response to ischemic injury. However, little is known about the mechanism...
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MDPI AG
2017-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/18/3/565 |
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| author | Shuai Yang Xinmei Zhao Hui Xu Fan Chen Yitao Xu Zhe Li Daniel Sanchis Liang Jin Yubin Zhang Junmei Ye |
| author_facet | Shuai Yang Xinmei Zhao Hui Xu Fan Chen Yitao Xu Zhe Li Daniel Sanchis Liang Jin Yubin Zhang Junmei Ye |
| author_sort | Shuai Yang |
| collection | DOAJ |
| description | The AKT (protein kinase B, PKB) family has been shown to participate in diverse cellular processes, including apoptosis. Previous studies demonstrated that protein kinase B2 (AKT2−/−) mice heart was sensitized to apoptosis in response to ischemic injury. However, little is known about the mechanism and apoptotic signaling pathway. Here, we show that AKT2 inhibition does not affect the development of cardiomyocytes but increases cell death during cardiomyocyte ischemia. Caspase-dependent apoptosis of both the extrinsic and intrinsic pathway was inactivated in cardiomyocytes with AKT2 inhibition during ischemia, while significant mitochondrial disruption was observed as well as intracytosolic translocation of cytochrome C (Cyto C) together with apoptosis-inducing factor (AIF) and endonuclease G (EndoG), both of which are proven to conduct DNA degradation in a range of cell death stimuli. Therefore, mitochondria-dependent cell death was investigated and the results suggested that AIF and EndoG nucleus translocation causes cardiomyocyte DNA degradation during ischemia when AKT2 is blocked. These data are the first to show a previous unrecognized function and mechanism of AKT2 in regulating cardiomyocyte survival during ischemia by inducing a unique mitochondrial-dependent DNA degradation pathway when it is inhibited. |
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| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T01:26:00Z |
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| spelling | doaj.art-14197c06834540099f78844fccdeb3462022-12-22T03:53:39ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-03-0118356510.3390/ijms18030565ijms18030565AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac IschemiaShuai Yang0Xinmei Zhao1Hui Xu2Fan Chen3Yitao Xu4Zhe Li5Daniel Sanchis6Liang Jin7Yubin Zhang8Junmei Ye9State Key Laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, ChinaState Key Laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, ChinaCenter of Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, ChinaState Key Laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, ChinaState Key Laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaInstitut de Recerca Biomèdica de Lleida (IRBLLEIDA)—Universitat de Lleida, Edifici Biomedicina-I. Av. Rovira Roure, 80., 25198 Lleida, SpainState Key Laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, ChinaState Key Laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, ChinaState Key Laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, ChinaThe AKT (protein kinase B, PKB) family has been shown to participate in diverse cellular processes, including apoptosis. Previous studies demonstrated that protein kinase B2 (AKT2−/−) mice heart was sensitized to apoptosis in response to ischemic injury. However, little is known about the mechanism and apoptotic signaling pathway. Here, we show that AKT2 inhibition does not affect the development of cardiomyocytes but increases cell death during cardiomyocyte ischemia. Caspase-dependent apoptosis of both the extrinsic and intrinsic pathway was inactivated in cardiomyocytes with AKT2 inhibition during ischemia, while significant mitochondrial disruption was observed as well as intracytosolic translocation of cytochrome C (Cyto C) together with apoptosis-inducing factor (AIF) and endonuclease G (EndoG), both of which are proven to conduct DNA degradation in a range of cell death stimuli. Therefore, mitochondria-dependent cell death was investigated and the results suggested that AIF and EndoG nucleus translocation causes cardiomyocyte DNA degradation during ischemia when AKT2 is blocked. These data are the first to show a previous unrecognized function and mechanism of AKT2 in regulating cardiomyocyte survival during ischemia by inducing a unique mitochondrial-dependent DNA degradation pathway when it is inhibited.http://www.mdpi.com/1422-0067/18/3/565cardiomyocytesapoptosisprotein kinase B2 (AKT2)ischemiaapoptosis-inducing factor (AIF)endonuclease G (EndoG) |
| spellingShingle | Shuai Yang Xinmei Zhao Hui Xu Fan Chen Yitao Xu Zhe Li Daniel Sanchis Liang Jin Yubin Zhang Junmei Ye AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia International Journal of Molecular Sciences cardiomyocytes apoptosis protein kinase B2 (AKT2) ischemia apoptosis-inducing factor (AIF) endonuclease G (EndoG) |
| title | AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia |
| title_full | AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia |
| title_fullStr | AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia |
| title_full_unstemmed | AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia |
| title_short | AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia |
| title_sort | akt2 blocks nucleus translocation of apoptosis inducing factor aif and endonuclease g endog while promoting caspase activation during cardiac ischemia |
| topic | cardiomyocytes apoptosis protein kinase B2 (AKT2) ischemia apoptosis-inducing factor (AIF) endonuclease G (EndoG) |
| url | http://www.mdpi.com/1422-0067/18/3/565 |
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