HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Role of caveolin-3 and glucose transporter-4 in isoflurane-induced delayed cardiac protection.

AbstractBACKGROUND:
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.
AuthorsYasuo M Tsutsumi, Yoshitaka Kawaraguchi, Yousuke T Horikawa, Ingrid R Niesman, Michael W Kidd, Blake Chin-Lee, Brian P Head, Piyush M Patel, David M Roth, Hemal H Patel
JournalAnesthesiology (Anesthesiology) Vol. 112 Issue 5 Pg. 1136-45 (May 2010) ISSN: 1528-1175 [Electronic] United States
PMID20418694 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Cardiotonic Agents
  • Caveolin 3
  • Glucose Transporter Type 4
  • Isoflurane
Topics
  • Animals
  • Cardiotonic Agents (pharmacology, therapeutic use)
  • Caveolin 3 (deficiency, genetics, physiology)
  • Glucose Transporter Type 4 (physiology)
  • Ischemic Preconditioning, Myocardial (methods)
  • Isoflurane (pharmacology, therapeutic use)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardial Infarction (genetics, metabolism, prevention & control)
  • Myocardial Reperfusion Injury (genetics, metabolism, prevention & control)
  • Myocytes, Cardiac (drug effects, physiology, ultrastructure)
  • Random Allocation
  • Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: