• Yasuo M Tsutsumi, Rie Tsutsumi, Yousuke T Horikawa, Yoko Sakai, Eisuke Hamaguchi, Yoshihiro Ishikawa, Utako Yokoyama, Asuka Kasai, Noriko Kambe, and Katsuya Tanaka.
• Department of Anesthesiology, University of Tokushima, Tokushima, Japan. Electronic address: tsutsumi@tokushima-u.ac.jp.
• Life Sci. 2014 Apr 17;101(1-2):43-8.

AimsGeranylgeranylacetone (GGA) is commonly utilized to protect the gastric mucosa in peptic ulcer disease. Recently GGA has been shown to protect the myocardium from ischemia/reperfusion by activating heat shock proteins. However, the exact mechanism as to how GGA activates these protective proteins is unknown. Caveolae and caveolin-3 (Cav-3) have been implicated in ischemia, anesthetic, and opioid induced cardiac protection. Given the lipophilic nature of GGA it is our hypothesis that GGA induced cardiac protection requires caveolae and Cav-3.Main MethodsWe used an in vivo mouse model of ischemia-reperfusion injury and performed biochemical assays in excised hearts.Key FindingsGGA treated control mice revealed increased caveolae formation and caveolin-3 in buoyant fractions, mediating heat shock protein 70 activation. Furthermore, control mice treated with GGA were protected against ischemia/reperfusion injury whereas Cav-3 knockout (Cav-3 KO) mice were not. Troponin levels confirmed myocardial damage. Finally, Cav-3 KO mice treated with GGA were not protected against mitochondrial swelling whereas control mice had significant protection.SignificanceThis study showed that caveolae and caveolin-3 are essential in facilitating GGA induced cardiac protection by optimizing spatial and temporal signaling to the mitochondria.Copyright © 2014 Elsevier Inc. All rights reserved.

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