The association between neuronal nitric oxide synthase and neuronal sensitivity in the brain after brain injury.
The association between neuronal nitric oxide synthase and neuronal sensitivity in the brain after brain injury.
复制标题
脑损伤后神经元一氧化氮合酶与大脑神经元敏感性之间的关联。
DOI：
10.1111/j.1749-6632.2002.tb04071.x
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发表时间：
2002
影响因子：
5.2
通讯作者：
Valadka,Alex
中科院分区：
文献类型：
--
作者：
Liu,PhilipK;Robertson,ClaudiaS;Valadka,Alex
摘要：中枢神经系统损伤是美国致残的主要原因。神经元死亡是致残的原因之一。在这种类型的损伤存活的患者中，可以观察到不同程度的脑功能恢复。功能恢复的分子基础尚不清楚。临床观察和使用实验损伤模型的研究表明，几种代谢物在导致神经元变性的级联事件中起作用。细胞内ATP（能量来源）和pH值水平降低，而细胞外谷氨酸水平、细胞内钙离子水平和对RNA/DNA、蛋白质和脂质的氧化损伤增加。这些初始事件可能与能量衰竭和线粒体功能障碍有关，导致功能性或结构性脑损伤。已知受伤的大脑会表达即时早期基因。最近的研究表明，活性氧（ROS）会导致mRNA转录基因的损伤，这是内源性神经保护反应的一部分。尽管退化的蛋白质和脂质可能在严重损伤后显著导致坏死，但遗传物质的异常，如果不进行修复，会通过影响复制、转录和翻译，在各个层面上扰乱细胞功能。这些病变包括异常核酸，称为DNA （ODLs）或RNA （ORLs）的氧化病变。在这篇综述中，我们重点介绍了我们目前对神经元一氧化氮合酶在脑损伤后诱导的DNA和RNA修饰碱基形成中的各种作用，以及odl和orl如何影响细胞功能的了解。
Abstract:Injury to the central nervous system is the leading cause of disability in the United States. Neuronal death is one of the causes of disability. Among patients who survive this type of injury, various degrees of recovery in brain function are observed. The molecular basis of functional recovery is poorly understood. Clinical observations and research using experimental injury models have implicated several metabolites in the cascade of events that lead to neuronal degeneration. The levels of intracellular ATP (energy source) and pH are decreased, whereas levels of extracellular glutamate, intracellular calcium ions, and oxidative damage to RNA/DNA, protein, and lipid are increased. These initiating events can be associated with energy failure and mitochondrial dysfunction, resulting in functional or structural brain damage. The injured brain is known to express immediate early genes. Recent studies show that reactive oxygen species (ROS) cause lesions in genes from which mRNA is transcribed as part of the endogenous neuroprotective response. Although degenerating proteins and lipids may contribute to necrosis significantly after severe injury, abnormalities in genetic material, if not repaired, disturb cellular function at every level by affecting replication, transcription, and translation. These lesions include abnormal nucleic acids, known as oxidative lesions of DNA (ODLs) or of RNA (ORLs). In this review, we focus on our current understanding of the various effects of neuronal nitric oxide synthase on the formation of modified bases in DNA and RNA that are induced in the brain after injury, and how ODLs and ORLs affect cell function.