Decreased sarcolipin protein expression and enhanced sarco(endo)plasmic reticulum Ca2+ uptake in human atrial fibrillation.

Decreased sarcolipin protein expression and enhanced sarco(endo)plasmic reticulum Ca2+ uptake in human atrial fibrillation.
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DOI:
10.1016/j.bbrc.2011.05.113
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发表时间:
2011-06-24
影响因子:
3.1
通讯作者:
Babu, Gopal J.
Babu, Gopal J.
中科院分区:
生物学4区
文献类型:
--
作者:
Shanmugam, Mayilvahanan;Molina, Cristina E.;Gao, Shumin;Severac-Bastide, Renaud;Fischmeister, Rodolphe;Babu, Gopal J.

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肌磷脂(Sarcolipin,SLN)是心肌肌浆网(SR)Ca ~(2+)ATP酶的关键调节因子,主要表达于心房,介导β-肾上腺素能反应。研究表明,SLN mRNA表达在人类慢性心房颤动(AF)和主动脉带状小鼠心房中降低;然而,SLN蛋白在人类心房病理中的表达及其在心房SR Ca 2+摄取中的作用尚未阐明。在本研究中,我们确定了主要的SR钙处理蛋白的表达在心房的人AF患者和人类和小鼠模型的心力衰竭(HF)。结果发现,压力超负荷性心力衰竭小鼠心房肌SR Ca ~(2+)摄取通道和Ca ~(2+)释放通道蛋白的表达明显降低,而心室肌SR Ca ~(2+)摄取通道和Ca ~(2+)释放通道蛋白的表达无明显变化。在人AF和HF中,SLN蛋白的表达显著降低,而其他主要SR Ca 2+处理蛋白的表达没有改变。此外,我们发现,SR Ca 2+摄取显着增加,在人类AF。选择性下调sarcolipin和增强SR Ca 2+摄取在人类AF表明,SLN下调可能发挥重要作用,在心房病理异常细胞内Ca 2+循环。
Sarcolipin (SLN), a key regulator of cardiac sarco(endo)plasmic reticulum (SR) Ca2+ ATPase, is predominantly expressed in atria and mediates β-adrenergic responses. Studies have shown that SLN mRNA expression is decreased in human chronic atrial fibrillation (AF) and in aortic banded mouse atria; however, SLN protein expression in human atrial pathology and its role in atrial SR Ca2+ uptake are not yet elucidated. In the present study, we determined the expression of major SR Ca2+ handling proteins in atria of human AF patients and in human and in a mouse model of heart failure (HF). We found that the expression of SR Ca2+ uptake and Ca2+ release channel proteins are significantly decreased in atria but not in the ventricles of pressure-overload induced HF in mice. In human AF and HF, the expression of SLN protein was significantly decreased; whereas the expressions of other major SR Ca2+ handling proteins were not altered. Further, we found that the SR Ca2+ uptake was significantly increased in human AF. The selective downregulation of sarcolipin and enhanced SR Ca2+ uptake in human AF suggest that SLN downregulation could play an important role in abnormal intracellular Ca2+ cycling in atrial pathology.
N 末端的苏氨酸-5 可以调节心肌细胞中的肌磷脂功能。
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