Desflurane-induced and ischaemic postconditioning against myocardial infarction are mediated by Pim-1 kinase
Desflurane-induced and ischaemic postconditioning against myocardial infarction are mediated by Pim-1 kinase
Background
Anaesthetic-induced (APOST) and ischaemic postconditioning (IPOST) against myocardial infarction are mediated via phosphatidylinositol-3-kinase/Akt. Pim-1 kinase is acting downstream of Akt and has recently been demonstrated to enhance cardiomyocyte survival. We tested the hypothesis that both APOST and IPOST are mediated by Pim-1 kinase.
Methods
Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45-min coronary artery occlusion (CAO) and 3-h reperfusion. Animals received either no intervention, the Pim-1 kinase inhibitor II (10??g/g intraperitoneally) or its vehicle dimethy sulfoxide (10??l/g intraperitoneally). Three minutes prior to the end of CAO, 1.0 minimum alveolar concentration desflurane was administered for 18?min alone or in combination with Pim-1 kinase inhibitor II. IPOST was induced by three cycles of each 10-s ischaemia/reperfusion, and animals received either IPOST alone or in combination with Pim-1 kinase inhibitor II. Infarct size was determined with triphenyltetrazolium chloride and area at risk with Evans blue. Protein expression of Pim-1 kinase, Bad, phospho-BadSer112 and B-cell lymphoma 2 was determined using Western immunoblotting analysis.
Results
Infarct size in control animals (CON) was 46?±?3%. Dimethylsulfoxide (47?±?3%) and Pim-1 kinase inhibitor II (44?±?5%) did not significantly reduce infarct size. Desflurane (16?±?2%*; *P?<?0.05 vs. CON) and IPOST (21?±?2%*) significantly reduced infarct size compared with CON. Inhibition of Pim-1 kinase abolished desflurane-induced postconditioning (46?±?4%) and IPOST (44?±?5%). Western blot analysis revealed that only desflurane enhances phosphorylation of Bad at serine 112 that was abrogated by Pim-1 kinase inhibitor II.
Conclusion
These data suggest that Pim-1 kinase mediates both desflurane-induced postconditioning and IPOST in mice.
904-913
Stumpner, J.
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Smul, T.M.
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Redel, A.
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Hilz, T.
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Tischer-Zeitz, T.
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Eisenbarth, H.
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Schick, M.A.
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Kehl, F.
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Roewer, N.
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Lange, M.
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August 2012
Stumpner, J.
38d15fd7-ed71-4f49-83cd-1a3d8c985091
Smul, T.M.
8a408a61-e120-4034-9d98-42a54d1708f3
Redel, A.
ea441874-69a4-4bb0-868a-42acc0e58421
Hilz, T.
bd433855-5464-4164-93fc-ae4306ea1c92
Tischer-Zeitz, T.
52877d74-4705-4bb3-8186-910b0a9b5660
Eisenbarth, H.
41af3dcb-da48-402b-a488-49de88e64f0c
Schick, M.A.
42b6e0cc-b812-4352-a4bb-e81e4d5d3192
Kehl, F.
6062a6d7-efc0-4693-a9db-bce671b35b06
Roewer, N.
0b1e5282-fd2f-4a01-b72e-3a980457598d
Lange, M.
09bc39bc-5524-4826-8079-22ae450a4965
Stumpner, J., Smul, T.M., Redel, A., Hilz, T., Tischer-Zeitz, T., Eisenbarth, H., Schick, M.A., Kehl, F., Roewer, N. and Lange, M.
(2012)
Desflurane-induced and ischaemic postconditioning against myocardial infarction are mediated by Pim-1 kinase.
Acta Anaesthesiologica Scandinavica, 56 (7), .
(doi:10.1111/j.1399-6576.2012.02657.x).
(PMID:22385356)
Abstract
Background
Anaesthetic-induced (APOST) and ischaemic postconditioning (IPOST) against myocardial infarction are mediated via phosphatidylinositol-3-kinase/Akt. Pim-1 kinase is acting downstream of Akt and has recently been demonstrated to enhance cardiomyocyte survival. We tested the hypothesis that both APOST and IPOST are mediated by Pim-1 kinase.
Methods
Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45-min coronary artery occlusion (CAO) and 3-h reperfusion. Animals received either no intervention, the Pim-1 kinase inhibitor II (10??g/g intraperitoneally) or its vehicle dimethy sulfoxide (10??l/g intraperitoneally). Three minutes prior to the end of CAO, 1.0 minimum alveolar concentration desflurane was administered for 18?min alone or in combination with Pim-1 kinase inhibitor II. IPOST was induced by three cycles of each 10-s ischaemia/reperfusion, and animals received either IPOST alone or in combination with Pim-1 kinase inhibitor II. Infarct size was determined with triphenyltetrazolium chloride and area at risk with Evans blue. Protein expression of Pim-1 kinase, Bad, phospho-BadSer112 and B-cell lymphoma 2 was determined using Western immunoblotting analysis.
Results
Infarct size in control animals (CON) was 46?±?3%. Dimethylsulfoxide (47?±?3%) and Pim-1 kinase inhibitor II (44?±?5%) did not significantly reduce infarct size. Desflurane (16?±?2%*; *P?<?0.05 vs. CON) and IPOST (21?±?2%*) significantly reduced infarct size compared with CON. Inhibition of Pim-1 kinase abolished desflurane-induced postconditioning (46?±?4%) and IPOST (44?±?5%). Western blot analysis revealed that only desflurane enhances phosphorylation of Bad at serine 112 that was abrogated by Pim-1 kinase inhibitor II.
Conclusion
These data suggest that Pim-1 kinase mediates both desflurane-induced postconditioning and IPOST in mice.
Text
703B5D72-79BA-4171-ACEE-D8A79A343CDB.pdf
- Accepted Manuscript
More information
Accepted/In Press date: 11 January 2012
e-pub ahead of print date: 5 March 2012
Published date: August 2012
Organisations:
Psychology
Identifiers
Local EPrints ID: 384803
URI: http://eprints.soton.ac.uk/id/eprint/384803
ISSN: 0001-5172
PURE UUID: b0a10c25-f80f-478d-b1e8-4bed015619b1
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Date deposited: 13 Jan 2016 10:33
Last modified: 15 Mar 2024 03:51
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Contributors
Author:
J. Stumpner
Author:
T.M. Smul
Author:
A. Redel
Author:
T. Hilz
Author:
T. Tischer-Zeitz
Author:
H. Eisenbarth
Author:
M.A. Schick
Author:
F. Kehl
Author:
N. Roewer
Author:
M. Lange
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