PMID- 22117619
OWN - NLM
STAT- MEDLINE
DCOM- 20121203
LR  - 20211021
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 16
IP  - 8
DP  - 2012 Aug
TI  - The Akt1 isoform is an essential mediator of ischaemic preconditioning.
PG  - 1739-49
LID - 10.1111/j.1582-4934.2011.01491.x [doi]
AB  - Phosphatidyl-inositol-3-kinase (PI3K)-Akt pathway is essential for conferring 
      cardioprotection in response to ischaemic preconditioning (IPC) stimulus. 
      However, the role of the individual Akt isoforms expressed in the heart in 
      mediating the protective response to IPC is unknown. In this study, we 
      investigated the specific contribution of Akt1 and Akt2 in cardioprotection 
      against ischaemia-reperfusion (I-R) injury. Mice deficient in Akt1 or Akt2 were 
      subjected to in vivo regional myocardial ischaemia for 30 min. followed by 
      reperfusion for 2 hrs with or without a prior IPC stimulus. Our results show that 
      mice deficient in Akt1 were resistant to protection with either one or three 
      cycles of IPC stimulus (42.7 +/- 6.5% control versus 38.5 +/- 1.9% 1 chi IPC, N = 6, 
      NS; 41.4 +/- 6.3% control versus 32.4 +/- 3.2% 3 chi IPC, N = 10, NS). Western blot 
      analysis, performed on heart samples taken from Akt1(-/-) mice subjected to IPC, 
      revealed an impaired phosphorylation of GSK-3beta, a downstream effector of Akt, as 
      well as Erk1/2, the parallel component of the reperfusion injury salvage kinase 
      pathway. Akt2(-/-) mice, which exhibit a diabetic phenotype, however, were 
      amenable to protection with three but not one cycle of IPC (46.4 +/- 5.6% control 
      versus 35.9 +/- 5.0% in 1 chi IPC, N = 6, NS; 47.0 +/- 6.0% control versus 30.8 +/- 3.3% 
      in 3 chi IPC, N = 6; *P = 0.039). Akt1 but not Akt2 is essential for mediating a 
      protective response to an IPC stimulus. Impaired activation of GSK-3beta and Erk1/2 
      might be responsible for the lack of protective response to IPC in Akt1(-/-) 
      mice. The rise in threshold for protection in Akt2(-/-) mice might be due to 
      their diabetic phenotype.
CI  - (c) 2011 The Authors Journal of Cellular and Molecular Medicine (c) 2011 Foundation 
      for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
FAU - Kunuthur, Suma P
AU  - Kunuthur SP
AD  - The Hatter Cardiovascular Institute, The Institute of Cardiovascular Science, 
      University College London, London, UK.
FAU - Mocanu, Mihaela M
AU  - Mocanu MM
FAU - Hemmings, Brian A
AU  - Hemmings BA
FAU - Hausenloy, Derek J
AU  - Hausenloy DJ
FAU - Yellon, Derek M
AU  - Yellon DM
LA  - eng
GR  - MR/K002066/1/MRC_/Medical Research Council/United Kingdom
GR  - PG/09/106/28142/BHF_/British Heart Foundation/United Kingdom
GR  - RG/08/015/26411/BHF_/British Heart Foundation/United Kingdom
GR  - PG/09/106/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Isoenzymes)
RN  - EC 2.7.11.1 (Akt1 protein, mouse)
RN  - EC 2.7.11.1 (Akt2 protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Aging/pathology
MH  - Animals
MH  - Hemodynamics
MH  - Hyperglycemia/enzymology/pathology
MH  - Immunoblotting
MH  - *Ischemic Preconditioning, Myocardial
MH  - Isoenzymes/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocardial Infarction/enzymology/pathology/physiopathology
MH  - Myocardium/enzymology/pathology
MH  - Proto-Oncogene Proteins c-akt/deficiency/*metabolism
MH  - Signal Transduction
MH  - Survival Analysis
PMC - PMC3822687
EDAT- 2011/11/29 06:00
MHDA- 2012/12/10 06:00
PMCR- 2012/08/01
CRDT- 2011/11/29 06:00
PHST- 2011/11/29 06:00 [entrez]
PHST- 2011/11/29 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2012/08/01 00:00 [pmc-release]
AID - 10.1111/j.1582-4934.2011.01491.x [doi]
PST - ppublish
SO  - J Cell Mol Med. 2012 Aug;16(8):1739-49. doi: 10.1111/j.1582-4934.2011.01491.x.