Phospholamban ablation and compensatory responses in the mammalian heart
Phospholamban ablation and compensatory responses in the mammalian heart
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DOI：
10.1111/j.1749-6632.1998.tb08256.x
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Kranias, EG
中科院分区：
文献类型：
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作者：
Chu, GX;Ferguson, DG;Kranias, EG
受磷蛋白（Phospholamban）是心肌肌浆网中的一种低分子量磷蛋白，近年来通过在胚胎干细胞中靶向该蛋白的基因并产生受磷蛋白缺陷小鼠，阐明了受磷蛋白在体内的调节作用。受磷蛋白基因敲除小鼠的心脏收缩参数显著增强，对β-激动剂的反应减弱。受磷蛋白基因敲除小鼠的高动力心脏功能不伴有任何细胞结构异常或心脏肌浆网Ca ~（2+）-ATP酶、钙螯合蛋白、Na ~+-Ca ~（2+）交换蛋白或收缩蛋白表达水平的改变。此外，对β-激动剂的心脏反应的减弱不是由于受磷蛋白敲除心脏中其他关键心脏磷蛋白的磷酸化水平的改变。然而，受磷蛋白的消融与兰尼碱受体的下调相关，这表明心脏肌浆网Ca 2+摄取和Ca 2+释放之间的串扰发生在试图维持这些高动力受磷蛋白敲除心脏中的Ca 2+稳态。
Phospholamban is a low molecular weight phosphoprotein in cardiac sarcoplasmic reticulum, The regulatory role of phospholamban in vivo has recently been elucidated by targeting the gene of this protein in embryonic stem cells and generating phospholamban-deficient mice. The phospholamban knockout hearts exhibited significantly enhanced contractile parameters and attenuated responses to beta-agonists, The hyperdynamic cardiac function of the phospholamban knockout mice was not accompanied by any cytoarchitectural abnormalities or alterations in the expression levels of the cardiac sarcoplasmic reticulum Ca2+-ATPase, calsequestrin, Na+-Ca2+ exchanger, or the contractile proteins. Furthermore, the attenuation of the cardiac responses to beta-agonists was not due to alterations in the phosphorylation levels of the other key cardiac phosphoproteins in the phospholamban knockout hearts. However, ablation of phospholamban was associated with down-regulation of the ryanodine receptor, which suggests that a cross-talk between cardiac sarcoplasmic reticulum Ca2+ uptake and Ca2+ release occurred in an attempt to maintain Ca2+ homeostasis in these hyperdynamic phospholamban knockout hearts.