Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Shanghai Zhulian Intelligent Technology Ltd. Co., Shanghai 201323, China.
J Proteome Res. 2021 Jun 4;20(6):3305-3314. doi: 10.1021/acs.jproteome.1c00208. Epub 2021 May 17.
An untargeted multi-omics study implicated the potential dysregulation of fatty acid, nucleotide, and energy metabolism in the brainstems of spontaneously hypertensive rats (SHRs). A further quantitative exploration of the alterations in the metabolic pathways is necessary for a deep understanding of the central nervous system in SHRs. Targeted metabolic profiling of 40 fatty acids (PeptideAtlas: PASS01671) and 32 metabolites of nucleotides and energy metabolism (PeptideAtlas: PASS01672) and parallel reaction monitoring analysis of 5 proteins (PeptideAtlas: PASS01673) were performed on the brainstems of SHRs ( = 8, 11 weeks old) and normotensive Wistar rats ( = 8, age-matched) using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem MS. The targeted profiling results of metabolites and proteins revealed decreased polyunsaturated fatty acid (PUFA) synthesis with a significant downregulation of -11,14-eicosadienoic acid, -13,16-docosadienoic acid, and docosatetraenoate and impaired PUFA oxidation with the accumulation of γ-linolenate induced by the significantly downregulated expression of 2,4-dienoyl-CoA reductase ( < 0.05). Dysregulated GTP and ATP metabolism was observed, with significantly decreased GDP and ADP ( < 0.05) correlated with reduced GTPases of guanine nucleotide-binding protein subunit beta-1 (GNB1), transforming protein RhoA (RHOA), and Rho-related GTP-binding protein RhoB (RHOB) in the brainstem of SHRs. In addition, protein-arginine deiminase type-2 was significantly reduced in the brainstems of SHRs ( < 0.05). The aberrant PUFA and energy metabolism might help to explain the alterations in the brainstem of SHRs. The findings on both metabolites and proteins could provide systemic insights into the pathology basis of altered PUFA and energy metabolism in hypertension, especially in the central nervous system.
一项非靶向性多组学研究表明，自发性高血压大鼠（SHR）脑干中脂肪酸、核苷酸和能量代谢的潜在失调。为了深入了解 SHR 中枢神经系统，有必要对代谢途径的变化进行进一步的定量探索。使用气相色谱-质谱联用仪（GC-MS）和液相色谱-串联质谱联用仪（LC-MS/MS）对 SHR （n = 8，11 周龄）和正常血压 Wistar 大鼠（n = 8，年龄匹配）的脑干进行了 40 种脂肪酸（PeptideAtlas：PASS01671）和 32 种核苷酸和能量代谢代谢物（PeptideAtlas：PASS01672）的靶向代谢谱分析以及 5 种蛋白质（PeptideAtlas：PASS01673）的平行反应监测分析。代谢物和蛋白质的靶向分析结果显示，多不饱和脂肪酸（PUFA）合成减少，其中 -11,14-二十碳二烯酸、-13,16-二十二碳二烯酸和二十二碳四烯酸的表达显著下调，PUFA 氧化受损，γ-亚麻酸积累，这与 2,4-二烯酰基辅酶 A 还原酶（2,4-dienoyl-CoA reductase）表达显著下调有关（<0.05）。还观察到 GTP 和 ATP 代谢失调，与脑桥中鸟嘌呤核苷酸结合蛋白亚基β-1（GNB1）、转化蛋白 RhoA（RHOA）和 Rho 相关 GTP 结合蛋白 RhoB（RHOB）的 GTPase 减少相关的 GDP 和 ADP 显著降低（<0.05）。此外，SHR 脑桥中的蛋白精氨酸脱氨酶 2 型（protein-arginine deiminase type-2）显著减少（<0.05）。异常的 PUFA 和能量代谢可能有助于解释 SHR 脑桥的变化。代谢物和蛋白质的发现为高血压，尤其是中枢神经系统中改变的 PUFA 和能量代谢的病理基础提供了系统的见解。
