AIMS: Geranylgeranylacetone (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 METHODS: We used an in vivo mouse model of ischemia-reperfusion injury and performed biochemical assays in excised hearts. KEY FINDINGS: GGA 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. SIGNIFICANCE: This study showed that caveolae and caveolin-3 are essential in facilitating GGA induced cardiac protection by optimizing spatial and temporal signaling to the mitochondria.
AIMS: Geranylgeranylacetone (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 METHODS: We used an in vivo mouse model of ischemia-reperfusion injury and performed biochemical assays in excised hearts. KEY FINDINGS: GGA 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. SIGNIFICANCE: This study showed that caveolae and caveolin-3 are essential in facilitating GGA induced cardiac protection by optimizing spatial and temporal signaling to the mitochondria.
Authors: Jan M Schilling; Yousuke T Horikawa; Alice E Zemljic-Harpf; Kevin P Vincent; Leonid Tyan; Judith K Yu; Andrew D McCulloch; Ravi C Balijepalli; Hemal H Patel; David M Roth Journal: Basic Res Cardiol Date: 2016-03-29 Impact factor: 17.165
Authors: Felicia Carotenuto; Alessandra Costa; Maria Cristina Albertini; Marco Bruno Luigi Rocchi; Alexander Rudov; Dario Coletti; Marilena Minieri; Paolo Di Nardo; Laura Teodori Journal: Int J Med Sci Date: 2016-02-18 Impact factor: 3.738