School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China.
J Proteome Res. 2020 Oct 2;19(10):4114-4124. doi: 10.1021/acs.jproteome.0c00585. Epub 2020 Sep 15.
The brainstem, the core of the central nervous system, plays a vital role in controlling arterial blood pressure and its elevation of hypertension subtypes, especially essential hypertension. Integrative metabolic and proteomic profiling was performed on the brainstem samples of 11 week old spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar rats, using hydrophilic interaction liquid chromatography quadrupole/time-of-flight mass spectrometry (HILIC-Q/TOFMS) (PeptideAtlas: PASS01621) and nano-liquid chromatography-high-resolution-MS (nano-LC-high-resolution) combined with quantitative tandem mass tags (ProteomeXchange: PXD021210). The results showed a potentially significant measure of metabolic disorders in the brainstem of SHRs, including purine and pyrimidine metabolism and carnitine and acylcarnitine deficiency. By integrating the differential metabolites (VIP > 1 and < 0.1) with the differentially expressed proteins (>1.2-fold and < 0.05), the results revealed aberrant insulin signaling in the brainstem of SHRs, including reduced carnitine and acetylcarnitine; increased arginine; and increased flotillin-1 (FLOT1), hemoglobin subunit alpha-1/2, and hemoglobin subunit beta-2 proteins verified by the parallel reaction monitoring analysis (PeptideAtlas: PASS01622). The aberrant insulin signaling pathway in the brainstem of SHRs might help explain the correlation between essential hypertension and insulin resistance. These findings on the brainstem of SHRs could provide new insights into the dysregulation of the central nervous system in hypertension, especially as it relates to metabolite and protein levels.
脑干是中枢神经系统的核心，在控制动脉血压及其升高的高血压亚型（尤其是原发性高血压）方面起着至关重要的作用。对 11 周龄自发性高血压大鼠（SHR）和年龄匹配的正常血压 Wistar 大鼠的脑干样本进行了整合代谢和蛋白质组学分析，使用亲水相互作用液相色谱四极杆/飞行时间质谱（HILIC-Q/TOFMS）（PeptideAtlas：PASS01621）和纳升级液相色谱-高分辨率-MS（nano-LC-high-resolution）结合定量串联质量标签（ProteomeXchange：PXD021210）。结果表明，SHR 脑干中存在潜在的代谢紊乱，包括嘌呤和嘧啶代谢以及肉碱和酰基辅酶 A 缺乏。通过将差异代谢物（VIP > 1 和 < 0.1）与差异表达的蛋白质（>1.2 倍和 < 0.05）整合，结果表明 SHR 脑干中的胰岛素信号异常，包括肉碱和乙酰肉碱减少；精氨酸增加；以及平行反应监测分析（PeptideAtlas：PASS01622）验证的 flotillin-1（FLOT1）、血红蛋白亚基 alpha-1/2 和血红蛋白亚基 beta-2 蛋白增加。SHR 脑干中异常的胰岛素信号通路可能有助于解释原发性高血压与胰岛素抵抗之间的相关性。这些关于 SHR 脑干的发现可以为高血压中中枢神经系统失调提供新的见解，特别是在与代谢物和蛋白质水平相关时。
