THYROID HORMONE-INDUCED ALTERATIONS IN PHOSPHOLAMBAN PROTEIN EXPRESSION - REGULATORY EFFECTS ON SARCOPLASMIC-RETICULUM CA2+ TRANSPORT AND MYOCARDIAL RELAXATION
THYROID HORMONE-INDUCED ALTERATIONS IN PHOSPHOLAMBAN PROTEIN EXPRESSION - REGULATORY EFFECTS ON SARCOPLASMIC-RETICULUM CA2+ TRANSPORT AND MYOCARDIAL RELAXATION
复制标题
DOI：
10.1161/01.res.75.2.245
复制
发表时间：
1994-08-01
影响因子：
20.1
通讯作者：
EDES, I
中科院分区：
文献类型：
--
作者：
KISS, E;JAKAB, G;EDES, I
本研究旨在探讨磷蛋白在甲减和甲亢大鼠心脏中的变化及其对肌浆网钙摄取和左心功能的调节作用。甲减与基础左心功能降低(+dp/dt和-dp/dt)相关，而甲亢患者这些参数与正常心脏相比升高。甲状腺功能低下、正常和甲亢心脏匀浆对钙的最大摄取速率分别为12.8+/-1.1、15.5+/-1.2和21.4+/-1.4nmolCa2+/min，EC(50)分别为0.76+/-0.09、0.41+/-0.07和0.30+/-0.05mU/m ol/L。与正常组(100%)相比，甲减组磷蛋白相对组织水平升高(135%)，甲亢组(75%)降低(75%)。而SR Ca~(2+)-ATPase则呈相反趋势，在甲减心脏中降低(74%)，在甲亢心脏中升高(134%)。因此，磷蛋白与Ca~(2+)-ATPase的相对比值在甲减时最高，在甲亢时最低，这些变化与肌浆网钙摄取的EC(50)变化有关。0.1MU/L异丙肾上腺素对心脏的刺激表明，与正常心脏相比，甲亢心脏的松弛作用较弱，而甲减心脏的松弛作用较高，这与磷白蛋白水平的变化一致。刺激异丙肾上腺素引起的松弛速度的最大增加与这些心脏的磷蛋白/钙-三磷酸腺苷酶的相对比例的变化有关。这些结果表明，与不同甲状腺状态有关的磷蛋白水平的变化可能反映了(1)肌浆网钙摄取率、(2)肌浆网钙泵对钙离子的亲和力、(3)心肌松弛速度和(4)β-肾上腺素能激动剂刺激效应的变化。
The aim of the present study was to determine the changes in phospholamban protein levels and their regulatory effect on sarcoplasmic reticulum (SR) Ca2+ uptake and left ventricular function in hypothyroid and hyperthyroid rat hearts. Hypothyroidism was associated with decreases in basal left ventricular function (+dP/dt and -dP/dt), whereas in hyperthyroidism these parameters were elevated compared with values for euthyroid hearts. The maximal SR Ca2+ uptake rates were 12.8+/-1.1, 15.5+/-1.2, and 21.4+/-1.4 nmol Ca2+ per milligram per minute, and the EC(50) values for Ca2+ were 0.76+/-0.09, O.41+/-0.07, and 0.30+/-0.05 mu mol/L assayed in homogenates from hypothyroid, euthyroid, and hyperthyroid hearts, respectively. The relative tissue level of phospholamban was increased (135%) in hypothyroidism and decreased (75%) in hyperthyroidism compared with euthyroidism (100%). An opposite trend was observed for the SR Ca2+ ATPase, which was depressed (74%) in hypothyroid hearts but increased (134%) in hyperthyroid hearts. Consequently, the relative ratio of phospholamban to Ca2+-ATPase was highest in hypothyroid and lowest in hyperthyroid hearts, and these changes correlated with changes in the EC(50) of the SR Ca2+ uptake for Ca2+. Stimulation of hearts with 0.1 mu mol/L isoproterenol revealed that the relaxant effects were lower in hyperthyroid hearts and higher in hypothyroid hearts compared with euthyroid hearts, consistent with the alterations in the phospholamban levels. The maximal increases in the speed of relaxation, elicited by isoproterenol stimulation, correlated with the changes in the relative ratio of phospholamban to Ca2+-ATPase in these hearts. These findings indicate that alterations in phospholamban levels associated with various thyroid states may reflect alterations in (1) SR Ca2+ uptake rates, (2) the affinity of the SR Ca2+ pump for Ca2+, (3) the speed of relaxation of the myocardium, and (4) stimulatory effects by beta-adrenergic agonists.