title: Ellagic acid and gingerol, activators of the sarco-endoplasmic reticulum Ca²⁺-ATPase, ameliorate diabetes mellitus-induced diastolic dysfunction in isolated murine ventricular myocardia.
abstract: The effects of sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) activators, ellagic acid and gingerol, on the contraction and Ca(2+) transient were examined in isolated myocardia from streptozotocin-induced diabetic mice and compared with control mice. The time required for relaxation of the right ventricular free wall was significantly longer in streptozotocin-treated mice. The basal Ca(2+) concentration of isolated ventricular myocytes from streptozotocin-treated mice was significantly higher than those from control mice. The Ca(2+) transient decay rate was significantly lower in myocytes from streptozotocin-treated mice. Cyclopiazonic acid, a SERCA inhibitor, decreased the rate of relaxation and the rate of Ca(2+) transient decay; these effects were larger in control mice. Both ellagic acid and gingerol accelerated the rate of relaxation and the rate of Ca(2+) transient decay; these effects were larger in the streptozotocin-treated mice. The acceleration of relaxation by ellagic acid and gingerol was completely inhibited by cyclopiazonic acid. These results suggest that the diabetes mellitus-induced myocardial diastolic dysfunction is partly caused by reduction of SERCA function and can be ameliorated by SERCA activators.
authors.affiliation: Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Funabashi, Chiba 274-8510, Japan. iyuki@phar.toho-u.ac.jp
authors.forename: Iyuki
authors.initials: I
authors.lastname: Namekata
authors.forename: Shogo
authors.initials: S
authors.lastname: Hamaguchi
authors.forename: Yumi
authors.initials: Y
authors.lastname: Wakasugi
authors.forename: Minato
authors.initials: M
authors.lastname: Ohhara
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirota
authors.forename: Hikaru
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D002396:Catechols / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D004610:Ellagic Acid / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D002396:Catechols; D005233:Fatty Alcohols; D007211:Indoles; D004610:Ellagic Acid; C007845:gingerol; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid