Department of Molecular Medicine, Hamidiye Institute of Health Sciences, University of Health Sciences, Istanbul, Turkey.
Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University-Çapa, Istanbul, Turkey.
J Food Biochem. 2021 Oct;45(10):e13923. doi: 10.1111/jfbc.13923. Epub 2021 Sep 8.
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. PRACTICAL APPLICATIONS: Ketosis is a potentially beneficial metabolic state for health especially in neurological conditions including Parkinson's disease (PD). Medium-chain-triglycerides (MCT) (C6-C12) have specific metabolic properties making them described as ketogenic even without restriction of carbohydrate. Octanoic acid (caprylic acid, C8) is the main MCT showing this effect. Our findings might help in the formulation of effective therapeutic strategies for the treatment of Parkinson's disease using ketogenic formulations involving Medium-chain-triglycerides.
酮症是一种对健康有益的代谢状态，特别是在包括帕金森病（PD）在内的神经疾病中。中链甘油三酯（MCT）具有特殊的代谢特性，即使不限制碳水化合物，它们也被描述为生酮的。辛酸（C8）是主要的 MCT，具有这种作用。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鉴定和定量磷酸蛋白质来发现特殊分子途径中的特定信号事件。鱼藤酮介导的生物学过程中的信号网络以及 MCT 对神经退行性疾病的有益影响尚不清楚。我们旨在全面了解鱼藤酮暴露的斑马鱼中使用辛酸处理后的全球磷酸蛋白质组差异的分子视角。从 MS 分析获得的原始文件经过处理，并使用 SEQUEST-HT 算法搜索 Danio rerio 蛋白质数据库进行鉴定和定量磷酸肽，共鉴定出 2,569 个独特的磷酸蛋白质和 4,161 个独特的磷酸肽，对应 2005 个蛋白质。鱼藤酮组中微管相关蛋白（MAP）家族成员显著降低。在鱼藤酮组中，涉及离子结合（钙、镁、锌离子）、氧结合、微管结合、ATP 和 GTP 结合的磷酸蛋白质是差异表达的 347 个蛋白质之一，在辛酸处理后得到逆转。鉴定了磷酸蛋白质和磷酸化位点，为进一步研究鱼藤酮毒性相关的信号通路提供了依据。我们相信，我们的研究结果可能有助于制定使用涉及 MCT 的生酮制剂治疗 PD 的有效治疗策略。实际应用：酮症是一种对健康有益的代谢状态，特别是在包括帕金森病（PD）在内的神经疾病中。中链甘油三酯（MCT）（C6-C12）具有特殊的代谢特性，即使不限制碳水化合物，它们也被描述为生酮的。辛酸（caprylic acid，C8）是主要的 MCT，具有这种作用。我们的研究结果可能有助于制定使用涉及 MCT 的生酮制剂治疗帕金森病的有效治疗策略。
