Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Neurochem. 2010 Dec;115(6):1322-36. doi: 10.1111/j.1471-4159.2010.07055.x. Epub 2010 Nov 19.
Lipids, particularly phospholipids, are fundamental to CNS tissue architecture and function. Endogenous polyunsaturated fatty acid chains of phospholipids possess cis-double bonds each separated by one methylene group. These phospholipids are very susceptible to free-radical attack and oxidative modifications. A combination of analytical methods including different versions of chromatography and mass spectrometry allows detailed information to be obtained on the content and distribution of lipids and their oxidation products thus constituting the newly emerging field of oxidative lipidomics. It is becoming evident that specific oxidative modifications of lipids are critical to a number of cellular functions, disease states and responses to oxidative stresses. Oxidative lipidomics is beginning to provide new mechanistic insights into traumatic brain injury which may have significant translational potential for development of therapies in acute CNS insults. In particular, selective oxidation of a mitochondria-specific phospholipid, cardiolipin, has been associated with the initiation and progression of apoptosis in injured neurons thus indicating new drug discovery targets. Furthermore, imaging mass-spectrometry represents an exciting new opportunity for correlating maps of lipid profiles and their oxidation products with structure and neuropathology. This review is focused on these most recent advancements in the field of lipidomics and oxidative lipidomics based on the applications of mass spectrometry and imaging mass spectrometry as they relate to studies of phospholipids in traumatic brain injury.
脂质，特别是磷脂，对中枢神经系统组织的结构和功能至关重要。磷脂中内源性多不饱和脂肪酸链具有顺式双键，每个双键之间相隔一个亚甲基。这些磷脂非常容易受到自由基攻击和氧化修饰。结合包括不同版本的色谱法和质谱法在内的多种分析方法，可以获得有关脂质及其氧化产物的含量和分布的详细信息，从而构成了新兴的氧化脂质组学领域。越来越明显的是，脂质的特定氧化修饰对于许多细胞功能、疾病状态以及对氧化应激的反应至关重要。氧化脂质组学开始为创伤性脑损伤提供新的机制见解，这可能为急性中枢神经系统损伤的治疗方法的发展带来重大的转化潜力。特别是，线粒体特异性磷脂心磷脂的选择性氧化与受损神经元中细胞凋亡的启动和进展有关，从而为新的药物发现目标指明了方向。此外，成像质谱代表了一个令人兴奋的新机会，可以将脂质图谱及其氧化产物与结构和神经病理学相关联。本综述重点介绍了基于质谱和成像质谱应用的脂质组学和氧化脂质组学领域的最新进展，这些进展与创伤性脑损伤中磷脂的研究有关。
