Calcium uptake by sarcoplasmic reticulum and its modulation by cAMP-dependent phosphorylation in normal and failing human myocardium.

Calcium uptake by sarcoplasmic reticulum and its modulation by cAMP-dependent phosphorylation in normal and failing human myocardium.
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正常和衰竭的人心肌中肌浆网的钙摄取及其通过 cAMP 依赖性磷酸化的调节。

DOI:
10.1007/978-3-642-72474-9_23
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发表时间:
1992
影响因子:
9.5
通讯作者:
M. Movsesian
M. Movsesian
中科院分区:
医学1区
文献类型:
--
作者:
M. Movsesian

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在从特发性扩张型心肌病移植受体的衰竭心脏和肾脏供体的非衰竭心脏(其心脏无合适的受体可用)获得的左心室游离壁心肌制备的微粒体中,检查了心脏肌浆网的ATP依赖性、酒石酸盐支持的Ca 2+摄取。两组之间的Vmax、K0.5(对于Ca 2+)或基础Ca 2+摄取的恩希尔值无显著差异。与cAMP依赖性磷酸化的受磷蛋白相关的Ca 2+摄取的刺激可以通过与受磷蛋白的单克隆抗体孵育微粒体来再现。刺激由K0.5降低引起,Vmax或恩希尔无变化。与抗受磷蛋白单克隆抗体孵育后的钙摄取的刺激幅度在正常和衰竭心脏的制剂中是相同的。最后,肌浆网相关的cGMP抑制cAMP磷酸二酯酶活性在这些制剂的特点。稳态动力学和药理学敏感性的测量表明,这种活动是功能均匀的。衰竭和非衰竭心脏的制剂在Vmax和Km值或对西洛酰胺衍生物OPC 3911抑制的敏感性方面没有差异。这些观察结果表明,在衰竭的人心肌细胞内[Ca 2 +]调节的异常不能归因于肌浆网中Ca(2+)-转运ATP酶、受磷蛋白或cGMP-抑制的cAMP磷酸二酯酶的水平或功能的变化。
ATP-dependent, oxalate-supported Ca2+ uptake by cardiac sarcoplasmic reticulum was examined in microsomes prepared from left-ventricular free wall myocardium obtained from the explanted failing hearts of transplant recipients with idiopathic dilated cardiomyopathy and the non-failing hearts of kidney donors for whose hearts no suitable recipients were available. There were no significant differences between the two groups with respect to values for Vmax, K0.5 (for Ca2+) or nHill of basal Ca2+ uptake. The stimulation of Ca2+ uptake associated with cAMP-dependent phosphorylation of phospholamban could be reproduced by incubation of microsomes with a monoclonal antibody to phospholamban. Stimulation resulted from a decrease in K0.5, with no changes in Vmax or nHill. The magnitude of stimulation of Ca2+ uptake following incubation with anti-phospholamban monoclonal antibody was identical in preparations from normal and failing hearts. Finally, sarcoplasmic reticulum-associated cGMP-inhibited cAMP phosphodiesterase activity in these preparations was characterised. Measurement of steady-state kinetics and pharmacologic sensitivity indicated that this activity was functionally homogeneous. Preparations from failing and non-failing hearts did not differ with respect to either values for Vmax and Km or susceptibility to inhibition by the cilostamide derivative OPC 3911. These observations indicate that abnormalities in the regulation of intracellular [Ca2+] in failing human myocardium cannot be ascribed to changes in the level or function of the Ca(2+)-transporting ATPase, phospholamban or cGMP-inhibited cAMP phosphodiesterase in the sarcoplasmic reticulum.
特发性扩张型心肌病患者心脏肌浆网对 Ca2 的摄取。
DOI: 10.1161/01.res.65.4.1141
发表时间: 1989
影响因子: 20.1
作者:
Movsesian,MA;Bristow,MR;Krall,J
通讯作者: Krall,J
DOI: 10.1172/jci113569
发表时间: 1988-07-01
影响因子: 15.9
作者:
FELDMAN, AM;CATES, AE;VANDOP, C
通讯作者: VANDOP, C
DOI: --
发表时间: 1989-03
影响因子: 3.6
作者:
M. Bristow;R. Hershberger;J. Port;W. Minobe;R. Rasmussen
通讯作者: M. Bristow;R. Hershberger;J. Port;W. Minobe;R. Rasmussen
DOI: 10.1161/01.res.61.1.70
发表时间: 1987-07-01
影响因子: 20.1
作者:
GWATHMEY, JK;COPELAS, L;MORGAN, JP
通讯作者: MORGAN, JP