Proteome Profiling of Cerebral Vessels in Rhesus Macaques: Dysregulation of Antioxidant Activity and Extracellular Matrix Proteins Contributes to Cerebrovascular Aging in Rhesus Macaques
Proteome Profiling of Cerebral Vessels in Rhesus Macaques: Dysregulation of Antioxidant Activity and Extracellular Matrix Proteins Contributes to Cerebrovascular Aging in Rhesus Macaques
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恒河猴脑血管的蛋白质组分析：抗氧化活性和细胞外基质蛋白的失调导致恒河猴脑血管老化
DOI：
10.3389/fnagi.2019.00293
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发表时间：
2019-10
影响因子：
4.8
通讯作者：
Ge Wei
中科院分区：
文献类型：
--
作者：
Wang Xia;Liu Yifan;Jia Yangjie;Liu Haotian;Bao Xinjie;He Zhanlong;Ge Wei
衰老是脑血管疾病的主要危险因素；然而，脑血管衰老的分子机制仍有待阐明。本研究的目的是揭示脑血管衰老中涉及的分子信号通路。本研究使用高分辨率液相色谱与串联质谱联用 (LC-MS/MS)，结合定量 6 重串联质量标签标记，来分析三组健康恒河猴（3 岁、6 岁和 20 岁）脑血管中的蛋白质变化。蛋白质印迹分析用于验证蛋白质组数据。总共鉴定并分析了 2,934 个蛋白质。随着年龄的增长，22种蛋白质持续下调，而3种蛋白质持续上调。当比较 C 组与 B 组时，270 个蛋白质下调，而 73 个蛋白质上调。所有这 368 个显着变化的蛋白质均用于进一步分析。生物信息分析表明，变化的蛋白质参与脑血管衰老过程中的多个信号通路。 NRF2 通路中的蛋白质，例如谷胱甘肽 S-转移酶 Mu (GSTM)，持续下调，尤其是在 6 岁之后，而与细胞外基质 (ECM) 和膜受体中 miRNA 靶标相关的蛋白质则上调。蛋白质-蛋白质相互作用网络表明，能量途径和丝氨酸/苏氨酸激酶的紊乱在脑血管衰老过程中至关重要。数据可通过 ProteomeXchange 获得，标识符为 PXD012306。我们的研究结果表明，衰老过程中，能量代谢紊乱和抗氧化活性功能障碍导致活性氧（ROS）产生过多，可能会加剧脑血管衰老。此外，衰老过程中 ECM 蛋白的积累可能与年龄相关的动脉硬化和顺应性下降密切相关。
Aging is a major risk factor for cerebrovascular disease; however, the molecular mechanisms of cerebrovascular aging remain to be clarified. The aim of this study was to reveal the molecular signaling pathways involved in cerebrovascular aging. This study used high-resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in combination with quantitative 6-plex tandem mass tag labeling, to profile protein changes in brain vessels from three groups of healthy rhesus macaques (3-years, 6-years, and 20-years). Western blot analyses were used to validate the proteomic data. A total of 2,934 proteins were identified and analyzed. Twenty-two proteins were continuously downregulated with increasing age, while three proteins were continuously upregulated. When comparing Group C vs. Group B, 270 proteins were downregulated, while 73 proteins were upregulated. All these 368 significantly changed proteins were used for further analysis. Bioinformatic analysis showed that the changed proteins were involved in several signaling pathways during cerebrovascular aging. Proteins in the NRF2 pathway, such as Glutathione S-transferase Mu (GSTM), were consistently downregulated especially after 6-years old, whereas proteins related to miRNA targets in the extracellular matrix (ECM) and membrane receptors were upregulated. Protein-protein interaction networks demonstrated that disorders of energy pathways and serine/threonine kinases were critical during cerebrovascular aging. Data are available via ProteomeXchange under the identifier PXD012306. Our results indicated that during aging, the disorders of energy metabolism and dysfunction of antioxidant activity caused over-production of reactive oxygen species (ROS) may exacerbate cerebrovascular aging. In addition, accumulation of ECM proteins during aging might be closely associated with age-related arterial stiffening and decreased compliance.
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影响因子：
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作者：
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影响因子：
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