C-terminal truncation of cardiac troponin I causes divergent effects on ATPase and force - Implications for the pathophysiology of myocardial stunning
C-terminal truncation of cardiac troponin I causes divergent effects on ATPase and force - Implications for the pathophysiology of myocardial stunning
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DOI：
10.1161/01.res.0000099889.35340.6f
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发表时间：
2003-11-14
影响因子：
20.1
通讯作者：
Van Eyk, JE
中科院分区：
文献类型：
--
作者：
Foster, DB;Noguchi, T;Van Eyk, JE
心肌顿抑是可逆性心肌缺血/再灌注损伤的一种形式，与收缩和舒张功能障碍有关。在离体大鼠心脏模型中，心肌顿抑的特征是肌丝蛋白肌钙蛋白I（cTnI）的特异性C-末端蛋白水解，产生cTnI（1-193）。为了确定cTnI的这种特定C-末端截短的影响，而不考虑其他休克诱导蛋白质修饰的混杂因素，使用小鼠/大鼠cTnI（1-193）的人类同源物cTnI（1-192）进行了一系列溶液生化测定。亲和层析和肌动蛋白沉降实验检测到cTnI（cTnI（1-209））和cTnI（1-192）与肌动蛋白原肌球蛋白、肌钙蛋白T或肌钙蛋白C的结合之间几乎没有差异。cTnI和cTnI（1-192）均抑制肌球蛋白亚片段1（S1）的肌动蛋白-原肌球蛋白激活的ATP酶活性，并且这种抑制作用在Ca 2+存在时由肌钙蛋白C释放。然而，与用cTnI（cTnI）重建的肌钙蛋白（cTnI）（1 - 192）相比，cTnI（1 - 192）作为肌钙蛋白复合物（cTnI（1-192））的一部分重建时，导致最大Ca 2+激活肌动蛋白-原肌球蛋白-S1 ATP酶活性增加54+/-11%。此外，与cTn相比，cTn（1-192）在体外运动试验中增加了肌动蛋白原肌球蛋白激活的S1 ATP酶活性的Ca 2+敏感性和重构细丝的Ca 2+依赖性滑动速度。在体外力测定中，携带cTn（1-192）的肌动蛋白原肌球蛋白细丝仅发育76+/-4%（P
Myocardial stunning is a form of reversible myocardial ischemia/reperfusion injury associated with systolic and diastolic contractile dysfunction. In the isolated rat heart model, myocardial stunning is characterized by specific C-terminal proteolysis of the myofilament protein, troponin I (cTnI) that yields cTnI(1-193). To determine the effect of this particular C-terminal truncation of cTnI, without the confounding factor of other stunning-induced protein modifications, a series of solution biochemical assays has been undertaken using the human homologue of mouse/rat cTnI(1-193), cTnI(1-192). Affinity chromatography and actin sedimentation experiments detected little, or no, difference between the binding of cTnI (cTnI(1-209)) and cTnI(1-192) to actin-tropomyosin, troponin T, or troponin C. Both cTnI and cTnI(1-192) inhibit the actin-tropomyosin-activated ATPase activity of myosin subfragment 1 (S1), and this inhibition is released by troponin C in the presence of Ca2+. However, cTnI(1-192), when reconstituted as part of the troponin complex (cTn(1-192)), caused a 54+/-11% increase in the maximum Ca2+-activated actin-tropomyosin-S1 ATPase activity, compared with troponin reconstituted with cTnI (cTn). Furthermore, cTn(1-192) increased Ca2+ sensitivity of both the actin-tropomyosin-activated S1 ATPase activity and the Ca2+-dependent sliding velocity of reconstituted thin filaments, in an in vitro motility assay, compared with cTn. In an in vitro force assay, the actin-tropomyosin filaments bearing cTn(1-192) developed only 76+/-4% (P