التفاصيل البيبلوغرافية
| العنوان: |
Oestrogen confers cardioprotection by suppressing Ca2+/calmodulin-dependent protein kinase II. |
| المؤلفون: |
Ma, Y.1, Cheng, W. T.1, Wu, S.1, Wong, T. M.1,2 wongtakm@hkucc.hku.hk |
| المصدر: |
British Journal of Pharmacology. Jul2009, Vol. 157 Issue 5, p705-715. 11p. 1 Chart, 6 Graphs. |
| مصطلحات موضوعية: |
*STEROID hormones, *PROTEIN kinases, *LACTATE dehydrogenase, *ESTROGEN, *PHOSPHOTRANSFERASES, *CALCIUM-binding proteins, *BIOLOGICAL models, *BIOCHEMISTRY, *ADRENERGIC beta agonists, *RESEARCH, *CELL culture, *CONVALESCENCE, *ISOPROTERENOL, *ANIMAL experimentation, *PROTEIN kinase inhibitors, *RESEARCH methodology, *MYOCARDIAL infarction, *CONTROLLED release drugs, *BETA adrenoceptors, *CARDIAC contraction, *APOPTOSIS, *MEDICAL cooperation, *EVALUATION research, *MYOCARDIAL reperfusion complications, *CELLULAR signal transduction, *RATS, *PHENOMENOLOGY, *AMINES, *COMPARATIVE studies, *CELLS, *OVARIECTOMY, *SULFONAMIDES, *PHOSPHORYLATION, *PHARMACODYNAMICS, *CHEMICAL inhibitors |
| مستخلص: |
Background and Purpose: Oestrogen confers cardioprotection by down-regulating the beta(1)-adrenoceptor and suppressing the expression and activity of protein kinase A. We hypothesized that oestrogen may also protect the heart by suppressing Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), another signalling messenger activated by the beta(1)-adrenoceptor, that enhances apoptosis.Experimental Approach: We first determined the expression of CaMKII in the heart from sham and ovariectomized rats with and without oestrogen replacement. We then determined the effects of CaMKII inhibition (KN93, 2.5 micromolxL(-1)) in the presence or absence of 10(-7) molxL(-1) isoprenaline, a non-selective beta-adrenoceptor agonist. We also determined the percentage apoptosis in myocytes from rats in each group with or without beta-adrenoceptor stimulation.Key Results: Both CaMKIIdelta and phosphorylated CaMKII were up-regulated in the hearts from ovariectomized rats, and they were restored to normal by oestrogen replacement. The infarct size and lactate dehydrogenase release were significantly greater after ovariectomy. Similarly, cardiac contractility, the amplitude of the electrically induced intracellular Ca(2+) transient and the number of apoptotic cells were also greater in ovariectomized rats upon ischaemia/reperfusion in the presence or absence of isoprenaline. Most importantly, the responses to ischaemic insult in ovariectomized rats were reversed not only by oestrogen replacement, but by blockade of CaMKII with KN93.Conclusions and Implications: Oestrogen confers cardioprotection at least partly by suppressing CaMKIIdelta. This effect of oestrogen on CaMKII is independent of the beta-adrenoceptor and occurs in addition to down-regulation of the receptor. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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