Publication: Hypersensitivity of myofilament response to Ca2+ in association with maladaptation of estrogen-deficient heart under diabetes complication
Issued Date
2007-02-01
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ISSN
15221490
03636119
03636119
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2-s2.0-33846817381
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Mahidol University
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SCOPUS
Bibliographic Citation
American Journal of Physiology - Regulatory Integrative and Comparative Physiology. Vol.292, No.2 (2007)
Suggested Citation
Ariyaporn Thawornkaiwong, Jantarima Pantharanontaga, Jonggonnee Wattanapermpool Hypersensitivity of myofilament response to Ca2+ in association with maladaptation of estrogen-deficient heart under diabetes complication. American Journal of Physiology - Regulatory Integrative and Comparative Physiology. Vol.292, No.2 (2007). doi:10.1152/ajpregu.00365.2006 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/24247
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Title
Hypersensitivity of myofilament response to Ca2+ in association with maladaptation of estrogen-deficient heart under diabetes complication
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Abstract
The amelioration of cardioprotective effect of estrogen in diabetes suggests potential interactive action of estrogen and insulin on myofilament activation. We compared Ca2+-dependent Mg2+-ATPase activity of isolated myofibrillar preparations from hearts of sham and 10-wk ovariectomized rats with or without simultaneous 8 wk-induction of diabetes and from diabetic-ovariectomized rats with estrogen and/or insulin supplementation. Similar magnitude of suppressed maximum myofibrillar ATPase activity was demonstrated in ovariectomized, diabetic, and diabetic-ovariectomized rat hearts. Such suppressed activity and the relative suppression in α-myosin heavy chain level in ovariectomy combined with diabetes could be completely restored by estrogen and insulin supplementation. Conversely, the myofilament Ca2+hypersensitivity detected only in the ovariectomized but not diabetic group was also observed in diabetic-ovariectomized rats, which was restored upon estrogen supplementation. Binding kinetics of β1- adrenergic receptors and immunoblots of β1-adrenoceptors as well as heat shock 72 (HSP72) were analyzed to determine the association of changes in receptors and HSP72 to that of the myofilament response to Ca2+. The amount of β1-adrenoceptors significantly increased concomitant with Ca2+hypersensitivity of the myofilament, without differences in the receptor binding affinity among the groups. In contrast, changes in HSP72 paralleled that of maximum myofibrillar ATPase activity. These results indicate that hypersensitivity of cardiac myofilament to Ca2+is specifically induced in ovariectomized rats even under diabetes complication and that alterations in the expression of β1-adrenoceptors may, in part, play a mechanistic role underlying the cardioprotective effects of estrogen that act together with Ca2+hypersensitivity of the myofilament in determining the gender difference in cardiac activation. Copyright © 2007 the American Physiological Society.