Role of caveolin-3 and glucose transporter-4 in isoflurane-induced delayed cardiac protection.
BACKGROUND
Caveolae are small, flask-like invaginations of the plasma membrane. Caveolins are structural proteins found in caveolae that have scaffolding properties to allow organization of signaling. The authors tested the hypothesis that delayed cardiac protection induced by volatile anesthetics is caveolae or caveolin dependent.


METHODS
An in vivo mouse model of ischemia-reperfusion injury with delayed anesthetic preconditioning (APC) was tested in wild-type, caveolin-1 knockout, and caveolin-3 knockout mice. Mice were exposed to 30 min of oxygen or isoflurane and allowed to recover for 24 h. After 24 h recovery, mice underwent 30-min coronary artery occlusion followed by 2 h of reperfusion at which time infarct size was determined. Biochemical assays were also performed in excised hearts.


RESULTS
Infarct size as a percent of the area at risk was reduced by isoflurane in wild-type (24.0 +/- 8.8% vs. 45.1 +/- 10.1%) and caveolin-1 knockout mice (27.2 +/- 12.5%). Caveolin-3 knockout mice did not show delayed APC (41.5 +/- 5.0%). Microscopically distinct caveolae were observed in wild-type and caveolin-1 knockout mice but not in caveolin-3 knockout mice. Delayed APC increased the amount of caveolin-3 protein but not caveolin-1 protein in discontinuous sucrose-gradient buoyant fractions. In addition, glucose transporter-4 was increased in buoyant fractions, and caveolin-3/glucose transporter-4 colocalization was observed in wild-type and caveolin-1 knockout mice after APC.


CONCLUSIONS
These results show that delayed APC involves translocation of caveolin-3 and glucose transporter-4 to caveolae, resulting in delayed protection in the myocardium.
Tsutsumi
Yasuo M
YM
Department of Anesthesiology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Kawaraguchi
Yoshitaka
Y
Horikawa
Yousuke T
YT
Niesman
Ingrid R
IR
Kidd
Michael W
MW
Chin-Lee
Blake
B
Head
Brian P
BP
Patel
Piyush M
PM
Roth
David M
DM
Patel
Hemal H
HH
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051244:Caveolin 3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051275:Glucose Transporter Type 4 / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D007530:Isoflurane / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D011897:Random Allocation; D013997:Time Factors
D002316:Cardiotonic Agents; D051244:Caveolin 3; D051275:Glucose Transporter Type 4; D007530:Isoflurane