title: Role of caveolin-3 and glucose transporter-4 in isoflurane-induced delayed cardiac protection.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yasuo M
authors.initials: YM
authors.lastname: Tsutsumi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kawaraguchi
authors.forename: Yousuke T
authors.initials: YT
authors.lastname: Horikawa
authors.forename: Ingrid R
authors.initials: IR
authors.lastname: Niesman
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kidd
authors.forename: Blake
authors.initials: B
authors.lastname: Chin-Lee
authors.forename: Brian P
authors.initials: BP
authors.lastname: Head
authors.forename: Piyush M
authors.initials: PM
authors.lastname: Patel
authors.forename: David M
authors.initials: DM
authors.lastname: Roth
authors.forename: Hemal H
authors.initials: HH
authors.lastname: Patel
mesh_terms: 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
chemical_list: D002316:Cardiotonic Agents; D051244:Caveolin 3; D051275:Glucose Transporter Type 4; D007530:Isoflurane