INCREASED COVALENT BINDING OF ACETALDEHYDE TO CALMODULIN IN THE PRESENCE OF CALCIUM
INCREASED COVALENT BINDING OF ACETALDEHYDE TO CALMODULIN IN THE PRESENCE OF CALCIUM
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DOI：
10.1016/0024-3205(89)90036-2
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发表时间：
1989-01-01
期刊：
影响因子：
6.1
通讯作者：
TUMA, DJ
中科院分区：
文献类型：
--
作者：
JENNETT, RB;SAFFARIFARD, A;TUMA, DJ
调节蛋白，钙调蛋白，在响应细胞内钙浓度的变化时经历了主要的构象变化。此外，据报道，钙调素具有赖氨酸残基，这显着增加了钙负载状态下对亲电物质的反应性。我们发现钙调素与乙醛在含钙状态下形成的加合物比无钙状态下稳定两到三倍。竞争结合研究表明，钙调蛋白可以优先与白蛋白竞争乙醛，而不是在没有钙的情况下。当钙调素处于载钙状态时，钙调素活性抑制剂三氟拉嗪显著降低乙醛与蛋白质的稳定结合，而在无钙状态下，对结合的影响最小。由于钙调素参与细胞中多个重要过程的调节，因此乙醛钙调素加合物可能通过扰乱肝细胞内钙依赖的稳态机制而导致肝损伤。
The regulatory protein, calmodulin, undergoes major conformational changes in response to changes in intracellular calcium concentration. Furthermore, calmodulin has been reported to have lysine residues which markedly increase their reactivity toward electrophilic substances in the calcium-loaded state. We found that calmodulin formed two to three times more stable adducts with acetaldehyde in the calcium-loaded state as compared to the calcium-free state. Competition-binding studies showed that calmodulin could preferentially compete with albumin for acetaldehyde in the presence, but not in the absence, of calcium. When calmodulin was in the calcium-loaded state, trifluoperazine, an inhibitor of calmodulin activity, significantly decreased the stable binding of acetaldehyde to the protein, whereas in the calcium-free state, minimal effects on binding were observed. Since calmodulin is involved in regulation of multiple important processes in the cell, it is possible that acetaldehyde-calmodulin adducts could contribute to liver injury by perturbation of calcium-dependent homeostatic mechanisms within the hepatocyte.