The role of protein O-linked beta-N-acetylglucosamine in mediating cardiac stress responses.
The role of protein O-linked beta-N-acetylglucosamine in mediating cardiac stress responses.
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DOI：
10.1016/j.bbagen.2009.07.004
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发表时间：
2010-02
影响因子：
3
通讯作者：
Marchase, Richard B.
中科院分区：
文献类型：
--
作者：
Chatham, John C.;Marchase, Richard B.
关键词：
O-linked β- n -乙酰氨基葡萄糖（O-GlcNAc）修饰核蛋白和细胞质蛋白的丝氨酸和苏氨酸残基是一种高度动态的翻译后修饰，在调节许多生物过程中起着关键作用。我们对O-GlcNAc在细胞功能中的作用机制的理解大多是在其介导一系列慢性疾病过程（包括糖尿病、癌症和神经退行性疾病）的不利影响的背景下进行的。然而，在细胞水平上，已经证明O-GlcNAc水平在应激反应中增加；这种反应的增强提高了细胞存活率，而衰减则降低了细胞活力。因此，很明显，提高O-GlcNAc水平的策略有利于细胞存活，而降低O-GlcNAc水平的策略会降低细胞存活。有很长的历史证明了急性葡萄糖-胰岛素-钾（GIK）治疗的有效性，以及在较小程度上谷氨酰胺对一系列应激的保护，包括心肌缺血。这些代谢性心脏保护方法的一个共同特点是它们都有可能刺激O-GlcNAc的合成。因此，我们研究了代谢性心脏保护与缺血性心脏保护与O-GlcNAc水平急性升高之间的联系。与o - glcn酰化激活相关的一些保护机制似乎是转录介导的；然而，也有强有力的证据表明，转录独立的机制也起着关键作用。在这种情况下，我们讨论了o - glcn酰化和心肌细胞钙稳态之间的潜在联系，包括非电压门控的作用，电容性钙进入作为促进这种保护的潜在机制。
The modification of serine and threonine residues of nuclear and cytoplasmic proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) has emerged as a highly dynamic post-translational modification that plays a critical role in regulating numerous biological processes. Much of our understanding of the mechanisms underlying the role of O-GlcNAc on cellular function has been in the context of its adverse effects in mediating a range of chronic disease processes, including diabetes, cancer and neurodegenerative diseases. However, at the cellular level it has been shown that O-GlcNAc levels are increased in response to stress; augmentation of this response improved cell survival while attenuation decreased cell viability. Thus, it has become apparent that strategies that augment O-GlcNAc levels are pro-survival, whereas those that reduce O-GlcNAc levels decrease cell survival. There is a long history demonstrating the effectiveness of acute glucose-insulin-potassium (GIK) treatment and to a lesser extent glutamine in protecting against a range of stresses, including myocardial ischemia. A common feature of these approaches for metabolic cardioprotection is that they both have the potential to stimulate O-GlcNAc synthesis. Consequently, here we examine the links between metabolic cardioprotection with the ischemic cardioprotection associated with acute increases in O-GlcNAc levels. Some of the protective mechanisms associated with activation of O-GlcNAcylation appear to be transcriptionally mediated; however, there is also strong evidence to suggest that transcriptionally independent mechanisms also play a critical role. In this context we discuss the potential link between O-GlcNAcylation and cardiomyocyte calcium homeostasis including the role of non-voltage gated, capacitative calcium entry as a potential mechanism contributing to this protection.
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