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首页> 美国卫生研究院文献>International Journal of Molecular Sciences >Post-Translational Protein Deimination Signatures in Serum and Serum-Extracellular Vesicles of Bos taurus Reveal Immune Anti-Pathogenic Anti-Viral Metabolic and Cancer-Related Pathways for Deimination
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Post-Translational Protein Deimination Signatures in Serum and Serum-Extracellular Vesicles of Bos taurus Reveal Immune Anti-Pathogenic Anti-Viral Metabolic and Cancer-Related Pathways for Deimination

机译：金牛血清和血清细胞外囊泡中的翻译后蛋白决定特征揭示了用于决定作用的免疫抗病原抗病毒代谢和癌症相关途径

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The bovine immune system is known for its unusual traits relating to immunoglobulin and antiviral responses. Peptidylarginine deiminases (PADs) are phylogenetically conserved enzymes that cause post-translational deimination, contributing to protein moonlighting in health and disease. PADs also regulate extracellular vesicle (EV) release, forming a critical part of cellular communication. As PAD-mediated mechanisms in bovine immunology and physiology remain to be investigated, this study profiled deimination signatures in serum and serum-EVs in . EVs were poly-dispersed in a 70–500 nm size range and showed differences in deiminated protein cargo, compared with whole sera. Key immune, metabolic and gene regulatory proteins were identified to be post-translationally deiminated with some overlapping hits in sera and EVs (e.g., immunoglobulins), while some were unique to either serum or serum-EVs (e.g., histones). Protein–protein interaction network analysis of deiminated proteins revealed KEGG pathways common for serum and serum-EVs, including complement and coagulation cascades, viral infection (enveloped viruses), viral myocarditis, bacterial and parasitic infections, autoimmune disease, immunodeficiency intestinal IgA production, B-cell receptor signalling, natural killer cell mediated cytotoxicity, platelet activation and hematopoiesis, alongside metabolic pathways including ferroptosis, vitamin digestion and absorption, cholesterol metabolism and mineral absorption. KEGG pathways specific to EVs related to HIF-1 signalling, oestrogen signalling and biosynthesis of amino acids. KEGG pathways specific for serum only, related to Epstein–Barr virus infection, transcription mis-regulation in cancer, bladder cancer, Rap1 signalling pathway, calcium signalling pathway and ECM-receptor interaction. This indicates differences in physiological and pathological pathways for deiminated proteins in serum-EVs, compared with serum. Our findings may shed light on pathways underlying a number of pathological and anti-pathogenic (viral, bacterial, parasitic) pathways, with putative translatable value to human pathologies, zoonotic diseases and development of therapies for infections, including anti-viral therapies.
机译：牛免疫系统因其与免疫球蛋白和抗病毒反应有关的非同寻常的特性而闻名。肽基精氨酸脱亚氨酶（PADs）是系统发育上保守的酶，可引起翻译后的脱端，从而促进蛋白质在健康和疾病中的表现。 PAD还调节细胞外囊泡（EV）释放，形成细胞通讯的关键部分。由于PAD介导的牛免疫学和生理学机制尚待研究，因此本研究概述了血清中血清和血清EV的决定信号。电动汽车多分散在70-500 nm的尺寸范围内，与整个血清相比，脱蛋白的蛋白质货物显示出差异。关键的免疫，代谢和基因调节蛋白被确定在翻译后被血清和EV重叠击中（例如免疫球蛋白），而某些则是血清或血清EV独特的（例如组蛋白）。蛋白质-蛋白质相互作用网络分析的最终蛋白质揭示了血清和血清电动汽车常见的KEGG途径，包括补体和凝血级联，病毒感染（包膜病毒），病毒性心肌炎，细菌和寄生虫感染，自身免疫性疾病，免疫缺陷性肠​​IgA产生，B -细胞受体信号转导，天然杀伤细胞介导的细胞毒性，血小板活化和造血作用，以及代谢途径，包括肥大症，维生素消化和吸收，胆固醇代谢和矿物质吸收。电动汽车特有的KEGG途径与HIF-1信号传导，雌激素信号传导和氨基酸的生物合成有关。仅针对血清的KEGG通路，与爱泼斯坦-巴尔病毒感染，癌症中的转录失调，膀胱癌，Rap1信号通路，钙信号通路和ECM受体相互作用有关。这表明与血清相比，血清电动汽车中脱蛋白的生理和病理学途径有所不同。我们的发现可能会揭示许多病理和抗病原性（病毒，细菌，寄生虫）途径的潜在途径，对人类病理学，人畜共患病以及包括抗病毒治疗在内的感染疗法的发展具有推定的价值。

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