PMID- 30165359
OWN - NLM
STAT- MEDLINE
DCOM- 20180918
LR  - 20191210
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 49
IP  - 2
DP  - 2018
TI  - PI3K-AKT Pathway Protects Cardiomyocytes Against Hypoxia-Induced Apoptosis by 
      MitoKATP-Mediated Mitochondrial Translocation of pAKT.
PG  - 717-727
LID - 10.1159/000493037 [doi]
AB  - BACKGROUND/AIMS: The phosphatidylinositol-3-kinase -AKT (PI3K-AKT) is an 
      important intracellular signal pathway in regulating cell proliferation, 
      differentiation and apoptosis. In previous studies, we've demonstrated that 
      PI3K-AKT pathway protects cardiomyocytes from ischemic and hypoxic apoptosis 
      through mitochondrial function. However, the molecular mechanisms underlying 
      hypoxia-induced cardiomyocyte apoptosis via PI3K-AKT pathway remain ill-defined. 
      Here, we addressed this question. METHODS: Cardiomyocytes were exposed to 
      hypoxia, with/without different inhibitors and then protein levels were assessed 
      by Western blotting. RESULTS: We found that the PI3K-AKT pathway was activated in 
      cardiomyocytes that were exposed to hypoxia. Moreover, the phospho-AKT (pAKT) 
      translocated from cytosol to mitochondria via mitochondrial adenosine 
      triphosphate-dependent potassium (mitoKATP), leading to an increase in cytochrome 
      c oxidase (CcO) activity to suppress apoptosis. On the other hand, the mitoKATP 
      specific blocker, 5-hydroxydecanote (5-HD), or suppression of CcO using siRNA, 
      inhibited the pAKT mitochondrial translocation to maintain the CcO activity, 
      resulting in mitochondrial dysfunction and cellular apoptosis induced by hypoxia. 
      CONCLUSION: These findings suggest that the anti-apoptotic effect of the PI3K-AKT 
      pathway through pAKT translocation to mitochondrial via mitoKATP may be conducted 
      through modification of CcO activity.
CI  - (c) 2018 The Author(s). Published by S. Karger AG, Basel.
FAU - Song, Hua-Pei
AU  - Song HP
AD  - Institute of Burns, State Key Laboratory of Trauma, Burn and Combined Injury, 
      South-west Hospital, Third Military Medical University, Chongqing, China.
FAU - Chu, Zhi-Gang
AU  - Chu ZG
AD  - Department of Burns, Tongren Hospital of Wuhan University & Wuhan Third Hospital, 
      Wuhan, China.
FAU - Zhang, Dong-Xia
AU  - Zhang DX
AD  - Institute of Burns, State Key Laboratory of Trauma, Burn and Combined Injury, 
      South-west Hospital, Third Military Medical University, Chongqing, China.
FAU - Dang, Yong-Ming
AU  - Dang YM
AD  - Institute of Burns, State Key Laboratory of Trauma, Burn and Combined Injury, 
      South-west Hospital, Third Military Medical University, Chongqing, China.
FAU - Zhang, Qiong
AU  - Zhang Q
AD  - Institute of Burns, State Key Laboratory of Trauma, Burn and Combined Injury, 
      South-west Hospital, Third Military Medical University, Chongqing, China.
LA  - eng
PT  - Journal Article
DEP - 20180830
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Chromones)
RN  - 0 (Decanoic Acids)
RN  - 0 (Hydroxy Acids)
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Potassium Channels)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (mitochondrial K(ATP) channel)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 624-00-0 (5-hydroxydecanoic acid)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - *Apoptosis/drug effects
MH  - Caspase 3/metabolism
MH  - *Cell Hypoxia
MH  - Cells, Cultured
MH  - Chromones/pharmacology
MH  - Decanoic Acids/pharmacology
MH  - Electron Transport Complex IV/antagonists & inhibitors/genetics/metabolism
MH  - Hydroxy Acids/pharmacology
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitochondria/metabolism
MH  - Morpholines/pharmacology
MH  - Myocytes, Cardiac/cytology/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Potassium Channels/chemistry/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Apoptosis
OT  - Cardiomyocytes
OT  - Hypoxic
OT  - MitoKATP
OT  - Mitochondrial
OT  - Pi3k-AKT
EDAT- 2018/08/31 06:00
MHDA- 2018/09/19 06:00
CRDT- 2018/08/31 06:00
PHST- 2018/02/20 00:00 [received]
PHST- 2018/08/21 00:00 [accepted]
PHST- 2018/08/31 06:00 [pubmed]
PHST- 2018/09/19 06:00 [medline]
PHST- 2018/08/31 06:00 [entrez]
AID - 000493037 [pii]
AID - 10.1159/000493037 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2018;49(2):717-727. doi: 10.1159/000493037. Epub 2018 Aug 
      30.