AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia
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Date
2017
Authors
Yang, Shuai
Zhao, Xinmei
Xu, Hui
Chen, Fan
Xu, Yitao
Li, Zhe
Sanchis, Daniel
Jin, Liang
Zhang, Yubin
Ye, Junmei
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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.
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International Journal of Molecular Sciences, 2017, vol. 18, núm. 565, p. 1-18