Quantitative phosphoproteomics to resolve the cellular responses to octanoic acid in rotenone exposed zebrafish,Journal of Food Biochemistry

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Quantitative phosphoproteomics to resolve the cellular responses to octanoic acid in rotenone exposed zebrafish
Journal of Food Biochemistry ( IF 3.5 ) Pub Date : 2021-09-08 , DOI: 10.1111/jfbc.13923
Mustafa Gani Sürmen ₁ , Saime Sürmen ₂ , Derya Cansız ₃ , İsmail Ünal ₄ , Ünsal Veli Üstündağ ₅ , Ahmet Ata Alturfan ₃ , Ebru Emekli-Alturfan ₆

Affiliation

Ketosis is a potentially beneficial metabolic state for health especially in neurological conditions including Parkinson’s disease (PD). Medium-chain-triglycerides (MCT) have specific metabolic properties and they are described as ketogenic even without restriction of carbohydrate. Octanoic acid (C8) is the main MCT showing this effect. Rotenone is a neurotoxin that is used to induce experimental PD model. Rotenone inhibits mitochondrial respiratory complex 1 (MRC1) and causes reactive oxygen species formation. Mass spectrometry (MS)-based phosphoproteomic methods enable discovering specific signaling events in special molecular pathways through identification and quantification of phosphoproteins. Signaling networks involved in rotenone-mediated biological processes and beneficial effects of MCTs on neurodegenerative diseases are not well understood. We aimed to gain comprehensive molecular perspective on the global phosphoproteome differences in rotenone-exposed zebrafish treated with octanoic acid. Raw files obtained from MS analysis were processed and searched against the Danio rerio protein database using SEQUEST-HT algorithm to identify and quantify phosphopeptides with 2,569 unique phosphoproteins and 4,161 unique phosphopeptides corresponding to 2005 proteins. Microtubule-associated protein (MAP) family members were significantly lower in rotenone group. Phosphoproteins involved in ion binding (calcium, magnesium, zinc ion), oxygen binding, microtubule binding, ATP- and GTP-binding were among differentially expressed 347 proteins in rotenone group and they were reversed after octanoic acid treatments. Phosphoproteins and phosphorylation sites were identified for future exploration of signaling pathways involved in rotenone toxicity. We believe our findings might help in the formulation of effective therapeutic strategies for the treatment of PD using ketogenic formulations involving MCTs.

中文翻译：

定量磷酸化蛋白质组学解决暴露于鱼藤酮的斑马鱼中对辛酸的细胞反应

酮症是一种潜在有益健康的代谢状态，尤其是在包括帕金森病 (PD) 在内的神经系统疾病中。中链甘油三酯 (MCT) 具有特定的代谢特性，即使不限制碳水化合物，它们也被描述为生酮。辛酸 (C8) 是显示此效果的主要 MCT。鱼藤酮是一种神经毒素，用于诱导实验性 PD 模型。鱼藤酮抑制线粒体呼吸复合物 1 (MRC1) 并导致活性氧的形成。基于质谱 (MS) 的磷酸蛋白质组学方法能够通过磷蛋白的识别和定量来发现特殊分子途径中的特定信号事件。鱼藤酮介导的生物过程中涉及的信号网络以及 MCT 对神经退行性疾病的有益作用尚不清楚。我们旨在获得关于用辛酸处理的鱼藤酮暴露斑马鱼的全球磷酸化蛋白质组差异的综合分子视角。使用 SEQUEST-HT 算法对从 MS 分析获得的原始文件进行处理和搜索，以识别和量化具有 2,569 种独特磷蛋白和 4,161 种与 2005 年蛋白质相对应的独特磷酸肽的磷酸肽。鱼藤酮组微管相关蛋白（MAP）家族成员显着降低。参与离子结合（钙、镁、锌离子）、氧结合、微管结合、ATP-和GTP-结合在鱼藤酮组中差异表达的347个蛋白质中，并且它们在辛酸处理后逆转。确定了磷蛋白和磷酸化位点，用于未来探索与鱼藤酮毒性有关的信号通路。我们相信我们的发现可能有助于制定有效的治疗策略，使用涉及 MCT 的生酮制剂治疗 PD。

更新日期：2021-10-06

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