Premium
The second window of desflurane‐induced preconditioning is mediated by STAT 3: role of Pim‐1 kinase
Author(s) -
Stumpner J.,
TischerZeitz T.,
Lotz C.,
Umminger J.,
Neuwirth A.,
Smul T. M.,
Redel A.,
Kehl F.,
Roewer N.,
Lange M.
Publication year - 2016
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/aas.12587
Subject(s) - medicine , desflurane , ischemic preconditioning , anesthesia , pentobarbital , kinase , stat3 , pharmacology , ischemia , signal transduction , isoflurane , chemistry , biochemistry
Background Late ischemic preconditioning is mediated via nuclear transcription factor signal transducer and activator of transcription 3 ( STAT 3). Pim‐1 kinase reduces infarct size in cardiomyocytes and is regulated by STAT 3. We tested the hypothesis that late desflurane‐induced preconditioning ( DES ‐ SWOP ) is mediated via STAT 3 and Pim‐1. Methods After institutional approval, pentobarbital‐anesthetized male C57 BL /6 mice were subjected to 45 min coronary artery occlusion ( CAO ) and 3 h reperfusion. Control animals received no additional intervention. Desflurane was administered 48 h before CAO either alone or in combination with the janus kinase/ STAT 3 inhibitor AG ‐490 (40 μg/g i.p., 20 min before desflurane administration) or the Pim‐1 kinase inhibitor II ( PIM ‐Inh. II , 10 μg/g i.p., 15 min before CAO ). Infarct size ( IS ) and area at risk were determined with triphenyltetrazolium chloride and Evans blue, respectively. Additionally, cytosolic and nuclear fractions were separated at two different time points and expression of STAT 3, phospho‐ STAT 3 Ser727 , phospho‐ STAT 3 Tyr705 , Pim‐1, Bad and phospho‐Bad Ser112 were determined by Western Blot analysis. Data were analyzed with one‐way or two‐way ANOVA and post hoc Duncan test and are presented as mean ± SEM. Results IS was 47 ± 2% ( n = 7–8 per group) in control animals ( CON ). DES ‐ SWOP reduced myocardial infarct size to 23 ± 4%* (* P < 0.05 vs. CON ). AG ‐490 alone did not affect myocardial infarct size (44 ± 7%), but abolished DES ‐ SWOP (44 ± 4%). Blockade of Pim‐1 did not affect the protection by DES ‐ SWOP (34 ± 4%*). Desflurane reduced cytosolic content and enhanced nuclear content of phospho‐ STAT S er727 . After 48 h, desflurane enhanced Pim‐1 activity, whereas Pim‐1 expression remained unchanged. Conclusion These data suggest that DES ‐ SWOP is mediated by activation and nuclear translocation of STAT 3. The impact of Pim‐1 in DES ‐ SWOP signaling remains unclear.