Centre de recherche du CHU de Québec, Faculty of Medicine, Université Laval, Québec City, Québec G1 V 4G2, Canada.
Proteomics Platform, Centre de recherche du CHU de Québec, Faculty of Medicine, Université Laval, Québec City, Québec G1 V 4G2, Canada.
J Proteome Res. 2021 Nov 5;20(11):5036-5053. doi: 10.1021/acs.jproteome.1c00542. Epub 2021 Oct 13.
A suboptimal blood vitamin C (ascorbate) level increases the risk of several chronic diseases. However, the detection of hypovitaminosis C is not a simple task, as ascorbate is unstable in blood samples. In this study, we examined the serum proteome of mice lacking the gulonolactone oxidase (Gulo) required for the ascorbate biosynthesis. mice were supplemented with different concentrations of ascorbate in drinking water, and serum was collected to identify proteins correlating with serum ascorbate levels using an unbiased label-free liquid chromatography-tandem mass spectrometry global quantitative proteomic approach. Parallel reaction monitoring was performed to validate the correlations. We uncovered that the serum proteome profiles differ significantly between male and female mice. Also, unlike males, a four-week ascorbate treatment did not entirely re-establish the serum proteome profile of ascorbate-deficient females to the optimal profile exhibited by females that never experienced an ascorbate deficiency. Finally, the serum proteins involved in retinoid metabolism, cholesterol, and lipid transport were similarly affected by ascorbate levels in males and females. In contrast, the proteins regulating serum peptidases and the protein of the acute phase response were different between males and females. These proteins are potential biomarkers correlating with blood ascorbate levels and require further study in standard clinical settings. The complete proteomics data set generated in this study has been deposited to the public repository ProteomeXchange with the data set identifier: PXD027019.
血液中维生素 C （抗坏血酸）水平不足会增加多种慢性疾病的风险。然而，检测抗坏血酸缺乏症并不简单，因为血液样本中的抗坏血酸不稳定。在这项研究中，我们检查了缺乏合成抗坏血酸所需的 gulonolactone 氧化酶（Gulo）的小鼠的血清蛋白质组。用不同浓度的抗坏血酸补充 小鼠，并收集血清，使用无偏液体色谱 - 串联质谱全局定量蛋白质组学方法鉴定与血清抗坏血酸水平相关的蛋白质。进行平行反应监测以验证相关性。我们发现雄性和雌性小鼠的血清蛋白质组谱差异显著。此外，与雄性小鼠不同，四周的抗坏血酸处理并不能将抗坏血酸缺乏的雌性小鼠的血清蛋白质组谱完全恢复到从未经历过抗坏血酸缺乏的雌性小鼠的最佳谱。最后，参与视黄醇代谢、胆固醇和脂质转运的血清蛋白也受到雄性和雌性抗坏血酸水平的类似影响。相比之下，调节血清肽酶和急性期反应蛋白的蛋白质在雄性和雌性之间存在差异。这些蛋白质是与血液抗坏血酸水平相关的潜在生物标志物，需要在标准临床环境中进一步研究。本研究中生成的完整蛋白质组数据集已存储在公共数据库 ProteomeXchange 中，数据集标识符为：PXD027019。
