Non-targeted profiling of lipids during kainate-induced neuronal injury
Non-targeted profiling of lipids during kainate-induced neuronal injury
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DOI：
10.1096/fj.05-5362com
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发表时间：
2006-06-01
期刊：
影响因子：
4.8
通讯作者：
Wenk, Markus R.
中科院分区：
文献类型：
--
作者：
Guan, Xue Li;He, Xin;Wenk, Markus R.
红藻氨酸盐是一种谷氨酸类似物，已广泛用于与缺血性疾病和癫痫相关的神经元损伤的药理学研究。虽然红藻氨酸盐的作用与脂质代谢的改变有关，但还没有研究在系统规模上研究脂质代谢物的相关变化。在这里，我们描述了一种基于质谱的方法，用于以非靶向方式分析脂质混合物。结合串联质谱法，该方法旨在鉴定在两种条件（红藻氨酸盐处理的海马组织和对照海马组织）之间改变的脂质。除了减少主要磷脂与主要是多不饱和脂肪酰基链，我们发现升高的离子水平，对应于磷脂酰乙醇胺和神经酰胺的酰化形式。酰化磷脂酰乙醇胺是神经保护性脂质和大麻酰胺的前体，大麻酰胺通过大麻素受体发出信号。神经酰胺的定量分析表明，在红藻氨酸盐处理过程中，许多具有不同酰基组成的分子种类增加。这种增加主要局限于神经元，而不是海马体中的其他脑细胞，如脑切片的免疫组织化学所揭示的。
Kainate is a glutamate analog that has been widely used in pharmacological studies of neuronal injury related to ischemic conditions and epilepsy. While altered lipid metabolism has been implicated in kainate action, no study has yet investigated the associated changes in lipid metabolites on a systems scale. Here we describe a mass spectrometry-based approach for profiling of lipid mixtures in a nontargeted fashion. Combined with tandem mass spectrometry, this method aims to identify lipids that are altered between two conditions, the kainate-treated and the control hippocampal tissues. In addition to reductions in major phospholipids with mainly polyunsaturated fatty acyl chains, we find elevated levels of ions that correspond to acylated forms of phosphatidylethanolamines and ceramides. Acylated phosphatidylethanolamines are neuroprotective lipids and precursors for anandamide, which signals via cannabinoid receptors. Quantitative analysis of ceramides shows that many molecular species with different acyl compositions are increased during kainate treatment. This increase is mainly restricted to neurons rather than other brain cells in the hippocampus as revealed by immunohistochemistry of brain slices.