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AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2017 Mar 06; Vol. 18 (3). Date of Electronic Publication: 2017 Mar 06. - Publication Year :
- 2017
-
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 <superscript>-/-</superscript> ) 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.
- Subjects :
- Active Transport, Cell Nucleus
Animals
Caspases metabolism
Cell Hypoxia
Cells, Cultured
Cytochromes c metabolism
DNA Fragmentation
HEK293 Cells
Humans
Mice
Mitochondria, Heart metabolism
Proto-Oncogene Proteins c-akt antagonists & inhibitors
Proto-Oncogene Proteins c-akt genetics
Rats
Rats, Sprague-Dawley
Apoptosis
Apoptosis Inducing Factor metabolism
Cell Nucleus metabolism
Endodeoxyribonucleases metabolism
Myocardial Ischemia metabolism
Myocytes, Cardiac metabolism
Proto-Oncogene Proteins c-akt metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 18
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 28272306
- Full Text :
- https://doi.org/10.3390/ijms18030565