Atrial chamber-specific expression of sarcolipin is regulated during development and hypertrophic remodeling
Atrial chamber-specific expression of sarcolipin is regulated during development and hypertrophic remodeling
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DOI：
10.1074/jbc.m213132200
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发表时间：
2003-03-14
影响因子：
4.8
通讯作者：
Matsuoka, R
中科院分区：
文献类型：
--
作者：
Minamisawa, S;Wang, YB;Matsuoka, R
细胞内Ca2+调节在正常心功能和病理性心脏的发展中是至关重要的。磷蛋白是肌浆网Ca2+ atp酶的内源性抑制剂，在心脏Ca2+循环中起重要作用。近年来，肌磷脂被认为在骨骼肌中具有与磷蛋白相似的功能。由于磷蛋白在心房和心室心肌中有差异表达，并且在病变心脏中表达经常发生改变，因此我们研究了肌磷脂表达的心腔特异性及其在发育和肥厚重塑过程中的调节。Northern blot分析显示，小鼠肌肽mRNA在心房中表达最丰富，在心室中检测不到，表明其具有心房特异性表达模式。在发育过程中，肌肽mRNA的心房特异性表达增加。这些发现被原位杂交研究证实。此外，在心室特异性过表达活化的H-ras基因诱导下，肥厚性心脏心房中肌磷脂的表达下调。在人类中，肌肽mRNA也在心房中表达，但在心室中未检测到，尽管肌肽mRNA在骨骼肌中表达最丰富。综上所述，肌肽可能是心脏Ca2+循环的心房特异性调节剂。
Intracellular Ca2+ regulation is critical in the normal cardiac function and development of pathologic hearts. Phospholamban, an endogenous inhibitor of sarcoplasmic reticulum Ca2+ ATPase in the sarcoplasmic reticulum, plays an important role in Ca2+ cycling in heart. Recently, sarcolipin has been identified as having a similar function as phospholamban in skeletal muscle. Because phospholamban is differentially expressed in atrial and ventricular myocardia and its expression is often altered in diseased hearts, we investigated the cardiac chamber specificity of sarcolipin expression and its regulation during development and hypertrophic remodeling. Northern blot analysis revealed that the expression of mouse sarcolipin mRNA was most abundant in the atria and was undetectable in the ventricles, indicating an atrial chamber-specific expression pattern. Atrial chamber-specific expression of sarcolipin mRNA was increased during development. These findings were confirmed by in situ hybridization studies. In addition, sarcolipin expression was down-regulated in the atria of hypertrophic heart when induced by ventricular specific overexpression of the activated H-ras gene. In humans, sarcolipin mRNA was also expressed in the atria but not detected in the ventricles, although sarcolipin expression was most abundant in skeletal muscle. Taken together, sarcolipin is likely to be an atrial chamber-specific regulator of Ca2+ cycling in heart.