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Int. J. Mol. Sci. 2017, 18(3), 565; doi:10.3390/ijms18030565

AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia

1
State Key Laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, China
2
Center of Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China
3
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
4
Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China
5
Hubei Key Laboratory of Cardiology, Wuhan 430060, China
6
Institut de Recerca Biomèdica de Lleida (IRBLLEIDA)—Universitat de Lleida, Edifici Biomedicina-I. Av. Rovira Roure, 80., 25198 Lleida, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Ritva Tikkanen
Received: 16 January 2017 / Revised: 13 February 2017 / Accepted: 23 February 2017 / Published: 6 March 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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. View Full-Text
Keywords: cardiomyocytes; apoptosis; protein kinase B2 (AKT2); ischemia; apoptosis-inducing factor (AIF); endonuclease G (EndoG) cardiomyocytes; apoptosis; protein kinase B2 (AKT2); ischemia; apoptosis-inducing factor (AIF); endonuclease G (EndoG)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Yang, S.; Zhao, X.; Xu, H.; Chen, F.; Xu, Y.; Li, Z.; Sanchis, D.; Jin, L.; Zhang, Y.; Ye, J. AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia. Int. J. Mol. Sci. 2017, 18, 565.

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