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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 mechanis...

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Autores principales: Yang, Shuai, Zhao, Xinmei, Xu, Hui, Chen, Fan, Xu, Yitao, Li, Zhe, Sanchis, Daniel, Jin, Liang, Zhang, Yubin, Ye, Junmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372581/
https://www.ncbi.nlm.nih.gov/pubmed/28272306
http://dx.doi.org/10.3390/ijms18030565
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author Yang, Shuai
Zhao, Xinmei
Xu, Hui
Chen, Fan
Xu, Yitao
Li, Zhe
Sanchis, Daniel
Jin, Liang
Zhang, Yubin
Ye, Junmei
author_facet Yang, Shuai
Zhao, Xinmei
Xu, Hui
Chen, Fan
Xu, Yitao
Li, Zhe
Sanchis, Daniel
Jin, Liang
Zhang, Yubin
Ye, Junmei
author_sort Yang, Shuai
collection PubMed
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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spelling pubmed-53725812017-04-10 AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia Yang, Shuai Zhao, Xinmei Xu, Hui Chen, Fan Xu, Yitao Li, Zhe Sanchis, Daniel Jin, Liang Zhang, Yubin Ye, Junmei Int J Mol Sci Article 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. MDPI 2017-03-06 /pmc/articles/PMC5372581/ /pubmed/28272306 http://dx.doi.org/10.3390/ijms18030565 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yang, Shuai
Zhao, Xinmei
Xu, Hui
Chen, Fan
Xu, Yitao
Li, Zhe
Sanchis, Daniel
Jin, Liang
Zhang, Yubin
Ye, Junmei
AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372581/
https://www.ncbi.nlm.nih.gov/pubmed/28272306
http://dx.doi.org/10.3390/ijms18030565
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