Ellagic acid and gingerol, activators of the sarco-endoplasmic reticulum Ca²⁺-ATPase, ameliorate diabetes mellitus-induced diastolic dysfunction in isolated murine ventricular myocardia

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• 作者：Iyuki Namekata ; ^{iyuki@phar.toho-u.ac.jp} ; Shogo Hamaguchi ; Yumi Wakasugi ; Minato Ohhara ; Yoshitaka Hirota ; Hikaru Tanaka
• 关键词：Sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) ; Diastolic dysfunction ; Diabetes
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：15 April, 2013
• 年：2013
• 卷：706
• 期：1-3
• 页码：48-55
• 全文大小：788 K

文摘

The effects of sarco-endoplasmic reticulum Ca²⁺-ATPase (SERCA) activators, ellagic acid and gingerol, on the contraction and Ca²⁺ 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 Ca²⁺ concentration of isolated ventricular myocytes from streptozotocin-treated mice was significantly higher than those from control mice. The Ca²⁺ 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 Ca²⁺ transient decay; these effects were larger in control mice. Both ellagic acid and gingerol accelerated the rate of relaxation and the rate of Ca²⁺ 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.