Coordinate regulation of SR Ca(2+)-ATPase and phospholamban expression in developing murine heart.
Coordinate regulation of SR Ca(2+)-ATPase and phospholamban expression in developing murine heart.
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发育中的小鼠心脏中 SR Ca(2 )-ATPase 和受磷蛋白表达的协调调节。
DOI：
10.1152/ajpheart.1997.272.1.h57
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Kranias,EG
中科院分区：
文献类型：
--
作者：
Harrer,JM;Haghighi,K;Kim,HW;Ferguson,DG;Kranias,EG
受磷蛋白是心肌肌浆网（SR）中Ca（2+）-腺苷三磷酸酶（ATP酶）活性的调节剂，是基础心肌功能的重要决定因素。为了确定受磷蛋白的表达是否在小鼠中受到发育调节，以及这种调节是否反映了Ca 2+泵活性的改变，对来自不同发育阶段的心脏进行了分子生物学和生物化学研究。受磷蛋白和Ca（2+）-ATP酶mRNA在出生时约为成人水平的40%（100%），并在发育第15天逐渐增加至接近成人水平。这些转录水平的变化表明受磷蛋白和Ca（2+）-ATP酶在蛋白水平上的变化。对Ca 2+摄取的初始速率的分析表明，在发育过程中，Ca（2+）-ATP酶的上调与Ca 2+摄取的最大速率的增加相关，受磷蛋白与Ca（2+）-ATP酶的恒定表观化学计量比与该酶对Ca 2+的恒定亲和力（0.25 +/- 0.03 μ M Ca 2+）的维持相关。此外，靶向消融小鼠受磷蛋白导致比野生型心脏中观察到的更高的Ca 2+摄取对Ca 2+的亲和力（0.10 +/- 0.02 microM Ca 2+），并且这种增加的亲和力也在出生后发育的不同阶段保持。这些发现表明受磷蛋白是Ca（2+）-ATPase对Ca（2+）亲和力的主要调节剂，这两种SR蛋白表达水平的协调调节可能是维持发育中哺乳动物心脏Ca（2+）稳态所必需的。
Phospholamban, the regulator of Ca(2+)-adenosinetriphosphatase (ATPase) activity in cardiac sarcoplasmic reticulum (SR), is an important determinant of basal myocardial performance. To determine whether phospholamban expression is developmentally regulated in the mouse and whether such regulation reflects alterations in Ca2+ pump activity, hearts from different stages of development were processed for molecular biological and biochemical studies. Both phospholamban and Ca(2+)-ATPase mRNAs were approximately 40% of adult (100%) levels at birth and gradually increased to approach adult levels by day 15 of development. These changes in transcript levels were indicative of changes at the protein level for both phospholamban and Ca(2+)-ATPase. Analysis of the initial rates of Ca2+ uptake demonstrated that over the course of development the upregulation of Ca(2+)-ATPase correlated with increases in the maximal rates of Ca2+ uptake and the constant apparent stoichiometric ratio of phospholamban to Ca(2+)-ATPase correlated with maintenance of a constant affinity of this enzyme for Ca2+ (0.25 +/- 0.03 microM Ca2+). Furthermore, targeted ablation of phospholamban in the mouse resulted in a much higher affinity of Ca2+ uptake for Ca2+ (0.10 +/- 0.02 microM Ca2+) than that observed in wild-type hearts, and this increased affinity was also maintained across different stages of postnatal development. These findings suggest that phospholamban is a major regulator of the affinity of Ca(2+)-ATPase for Ca2+, and coordinate regulation of the expression levels of these two SR proteins may be necessary for maintaining Ca2+ homeostasis in the developing mammalian heart.