Reactive carbonyl species and their roles in sarcoplasmic reticulum Ca2+ cycling defect in the diabetic heart.
Reactive carbonyl species and their roles in sarcoplasmic reticulum Ca2+ cycling defect in the diabetic heart.
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DOI：
10.1007/s10741-013-9384-9
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发表时间：
2014-01
影响因子：
4.6
通讯作者：
Bidasee KR
中科院分区：
文献类型：
--
作者：
Tian C;Alomar F;Moore CJ;Shao CH;Kutty S;Singh J;Bidasee KR
有效和有节律的心脏收缩依赖于肌浆网(SR)通过兰尼定受体钙释放通道(RyR2)和肌浆网钙-ATPase(SERCA2a)充分和同步地释放钙并重新摄取。众所周知，这一精心安排的过程在糖尿病患者中会受到影响。目前尚未完全明确的是糖尿病中RyR2和SERCA2a调控失调的分子机制。早些时候，研究人员发现，从1型糖尿病大鼠心脏分离的RyR2和SERCA2a上的羰基加合物水平升高，并表明这些翻译后修饰的存在损害了它们的功能。我们还表明，这些单和双羰基反应性羰基物种(RCS)不会不分青红皂白地与RyR2和SERCA2a上的所有碱性氨基酸残基反应；一些残基比其他残基更容易发生羰化(被RCS修饰)。该领域的一个关键悬而未决的问题是，糖尿病患者心脏中上调的许多RC中，哪些与RyR2和SERCA2a发生化学反应？这篇简短的综述向读者介绍了RCS的领域及其在扰乱糖尿病患者SR钙循环中的作用。它还提供了新的实验证据，表明并不是所有糖尿病患者心脏中上调的RCS都与RyR2和SERCA2a、甲基乙二醛和乙二醛发生化学反应。
Efficient and rhythmic cardiac contractions depend critically on the adequate and synchronized release of Ca2+ from the sarcoplasmic reticulum (SR) via ryanodine receptor Ca2+ release channels (RyR2) and its reuptake via sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a). It is well established that this orchestrated process becomes compromised in diabetes. What remain incompletely defined are the molecular mechanisms responsible for the dysregulation of RyR2 and SERCA2a in diabetes. Earlier, found elevated levels of carbonyl adducts on RyR2 and SERCA2a isolated from hearts of type 1 diabetic rats and showed the presence of these post-translational modifications compromised their functions. We also showed that these mono- and di-carbonyl reactive carbonyl species (RCS) do not indiscriminately react with all basic amino acid residues on RyR2 and SERCA2a; some residues are more susceptible to carbonylation (modification by RCS) than others. A key unresolved question in the field is which of the many RCS that are upregulated in the heart in diabetes chemically react with RyR2 and SERCA2a? This brief review introduces readers to the field of RCS and their roles in perturbing SR Ca2+ cycling in diabetes. It also provides new experimental evidence that not all RCS that are upregulated in the heart in diabetes chemically react with RyR2 and SERCA2a, methylglyoxal and glyoxal preferentially do.