Alterations in sarcoplasmic reticulum calcium-storing proteins in pressure-overload cardiac hypertrophy
Alterations in sarcoplasmic reticulum calcium-storing proteins in pressure-overload cardiac hypertrophy
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DOI：
10.1152/ajpheart.1997.272.1.h168
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发表时间：
1997-01-01
影响因子：
4.8
通讯作者：
Takeshita, A
中科院分区：
文献类型：
--
作者：
Tsutsui, H;Ishibashi, Y;Takeshita, A
细胞内钙（Ca2+）稳态的改变可能是压力过载心肌肥厚的收缩缺陷的原因。肌浆网（SR）的Ca2+-腺苷三磷酸酶（atp酶）蛋白水平在肥厚或衰竭的心脏中降低。然而，Ca2+储存蛋白，包括钙调磷酸酯蛋白和钙网蛋白，是否在心脏肥厚过程中也发生改变尚不清楚。我们使用Western blot方法对假手术对照大鼠（n = 6）和腹主动脉收缩后4周压力过载大鼠（n = 7）分离的左心室（LV）肌肉进行SR Ca2+调节蛋白的定量分析。用激光衍射测量肌节运动来评价主动脉收缩大鼠离体左室肌细胞的收缩功能。肥厚心肌SR Ca2+- atpase蛋白水平降至对照组的56 +/- 9% （P < 0.01）。主动脉收缩大鼠钙调磷酸酶（calsequestrin）蛋白水平无明显变化，而钙调磷酸酶（calreticulin）升高120±3% （P < 0.05）。即使使用每个样品中肌球蛋白重链蛋白的量将结果归一化，在肥厚的心脏中也同样观察到SR Ca2+调节蛋白的改变。对照心脏钙调钙素的免疫组化染色在Z线上显示交叉条纹，而钙调钙素在肌细胞中几乎没有观察到，但在间质成纤维细胞中表现强烈。在肥大的心脏中，心肌细胞胞浆内的核周区可见钙网蛋白。这些数据表明，压力过载心脏肥厚导致SR Ca2+储存蛋白以及Ca2+- atp酶的改变，这可能导致肥厚的肌细胞收缩功能障碍。
The alterations of intracellular calcium (Ca2+) homeostasis may be responsible for the contractile defects in pressure-overload cardiac hypertrophy. The Ca2+-adenosinetriphosphatase (ATPase) protein level of the sarcoplasmic reticulum (SR) is reduced in the hypertrophied or failing heart. However, it is not known whether Ca2+-storing proteins, including calsequestrin and calreticulin, are also altered during cardiac hypertrophy. We quantified SR Ca2+-regulatory proteins using Western blot analysis in left ventricular (LV) muscle isolated from sham-operated control rats (n = 6) and rats with pressure overload 4 wk after abdominal aortic constriction (n = 7). The contractile function of isolated LV myocytes, assessed by the sarcomere motion measured with laser diffraction, was depressed in aortic-constricted rats. The SR Ca2+-ATPase protein level was decreased to 56 +/- 9% (SE) of the control value in hypertrophied myocardium (P < 0.01). The calsequestrin protein level was not altered, whereas calreticulin was increased by 120 +/- 3% of the control value in aortic-constricted rats (P < 0.05). The alterations in SR Ca2+-regulatory proteins were equally observed in hypertrophied hearts even when the results were normalized using the amounts of myosin heavy chain proteins in each sample. Immunohistochemical staining of calsequestrin in the control heart showed cross striations at the Z Lines, whereas calreticulin was hardly observed within myocytes but was intense within interstitial fibroblasts. In the hypertrophied heart, calreticulin was observed at the perinuclear region within the myocyte cytoplasm. These data indicate that pressure-overload cardiac hypertrophy causes the alterations in SR Ca2+-storing proteins as well as in Ca2+-ATPase, which may contribute to the contractile dysfunction of the hypertrophied myocytes.