Lipidomics Analysis Reveals a Protective Effect of Myriocin on Cerebral Ischemia/Reperfusion Model Rats

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Molecular Neuroscience Pub Date : 2022-07-01 DOI:10.1007/s12031-022-02014-w

Ting Wang, Jingmin Zhang, Meng Yang, Jinxiu Guo, Duolu Li, Ying Li

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引用次数: 3

Abstract

Ceramide accumulation has been associated with ischemic stroke. Myriocin is an effective serine palmitoyltransferase (SPT) inhibitor that reduces ceramide levels by inhibiting the de novo synthesis pathway. However, the role of myriocin in cerebral ischemia/reperfusion (I/R) injury and its underlying mechanism remain unknown. The present study established an experimental rat model of middle cerebral artery occlusion (MCAO). We employed ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)–based lipidomic analysis to identify the disordered lipid metabolites and the effects of myriocin in cerebral cortical tissues of rats. In this study, we found 15 characterized lipid metabolites involved in sphingolipid and glycerophospholipid metabolism in cerebral I/R-injured rats, and these alterations were significantly alleviated by myriocin. Specifically, the mRNA expression of metabolism-related enzyme genes was detected by real-time quantitative polymerase chain reaction (RT-qPCR). We demonstrated that myriocin could regulate the mRNA expression of ASMase, NSMase, SGMS1, SGMS2, ASAH1, ACER2, and ACER3, which are involved in sphingolipid metabolism and PLA2, which is involved in glycerophospholipid metabolism. Moreover, TUNEL and Western blot assays showed that myriocin plays a key role in regulating neuronal cell apoptosis. In summary, the present work provides a new perspective for the systematic study of metabolic changes in ischemic stroke and the therapeutic applications of myriocin.

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脂质组学分析揭示肉豆蔻素对脑缺血再灌注模型大鼠的保护作用

神经酰胺积累与缺血性脑卒中有关。肉豆蔻素是一种有效的丝氨酸棕榈酰转移酶(SPT)抑制剂，通过抑制新生合成途径降低神经酰胺水平。然而，肉豆蔻素在脑缺血再灌注(I/R)损伤中的作用及其机制尚不清楚。本研究建立了大鼠大脑中动脉闭塞(MCAO)模型。采用超高效液相色谱-四极杆飞行时间质谱(UPLC-Q-TOF/MS)为基础的脂质组学分析方法，鉴定大鼠大脑皮质组织中紊乱的脂质代谢物及肉豆杉素的作用。本研究在脑I/ r损伤大鼠中发现了15种参与鞘脂和甘油磷脂代谢的特征性脂质代谢产物，肉豆蔻素可显著缓解这些改变。具体而言，通过实时定量聚合酶链反应(RT-qPCR)检测代谢相关酶基因的mRNA表达。我们发现肉豆蔻素可以调节参与鞘脂代谢的ASMase、NSMase、SGMS1、SGMS2、ASAH1、ACER2、ACER3和参与甘油磷脂代谢的PLA2的mRNA表达。此外，TUNEL和Western blot实验表明，肉豆蔻素在调节神经元细胞凋亡中起关键作用。综上所述，本研究为系统研究缺血性脑卒中的代谢变化及肉豆蔻素的治疗应用提供了新的视角。

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来源期刊

Journal of Molecular Neuroscience 医学-神经科学

CiteScore

6.60

自引率

3.20%

发文量

142

审稿时长

1 months

期刊介绍： The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.