The second window of desflurane‐induced preconditioning is mediated by STAT 3: role of Pim‐1 kinase

• Published in: Acta anaesthesiologica Scandinavica Vol. 60; no. 1; pp. 103 - 116
• Main Authors: Stumpner, J., Tischer‐Zeitz, T., Lotz, C., Umminger, J., Neuwirth, A., Smul, T. M., Redel, A., Kehl, F., Roewer, N., Lange, M.
• Format: Journal Article
• Language: English
• Published: 01-01-2016
• ISSN: 0001-5172; 1399-6576
• DOI: 10.1111/aas.12587

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.