Gautam Ghosh, Benjamin A. Neely, Alison M. Bland, Emily R. Whitmer, Cara L. Field, Pádraig J. Duignan and Michael G. Janech*,
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引用次数: 0
摘要
自 1998 年以来,加州海狮(Zalophus californianus)因多溴酸中毒(DAT)而搁浅的事件持续增加。除了在搁浅时直接测量体液中的多摩酸外,目前还没有实用的非致命性临床检测方法可用于诊断康复设施中的多摩酸中毒症。我们利用搁浅的患有急性多杀性海狮病(8 头)、慢性多杀性海狮病(19 头)或无多杀性海狮病(13 头)的加州海狮的脑脊液进行了蛋白质组学分析,以发现多杀性海狮病的候选蛋白质标记物。整个实验共鉴定出 2005 个蛋白质家族。共有 83 个蛋白质的丰度在三组中存在显著差异(adj. p < 0.05)。MDH1、PLD3、ADAM22、YWHAG、VGF 和 CLSTN1 可以区分有无 DAT 的加州海狮(AuROC > 0.75)。IGKV2D-28、PTRPF、KNG1、F2 和 SNCB 能够区分急性 DAT 和慢性 DAT(AuROC > 0.75)。参与α突触核蛋白沉积的蛋白质在DAT的分类中占有很大比例,其中许多蛋白质与多种神经退行性疾病有关。这些蛋白质应被视为加利福尼亚海狮 DAT 的潜在标记物,并应作为生物标记物优先用于未来的验证研究。
Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus)
Since 1998, California sea lion (Zalophus californianus) stranding events associated with domoic acid toxicosis (DAT) have consistently increased. Outside of direct measurement of domoic acid in bodily fluids at the time of stranding, there are no practical nonlethal clinical tests for the diagnosis of DAT that can be utilized in a rehabilitation facility. Proteomics analysis was conducted to discover candidate protein markers of DAT using cerebrospinal fluid from stranded California sea lions with acute DAT (n = 8), chronic DAT (n = 19), or without DAT (n = 13). A total of 2005 protein families were identified experiment-wide. A total of 83 proteins were significantly different in abundance across the three groups (adj. p < 0.05). MDH1, PLD3, ADAM22, YWHAG, VGF, and CLSTN1 could discriminate California sea lions with or without DAT (AuROC > 0.75). IGKV2D-28, PTRPF, KNG1, F2, and SNCB were able to discriminate acute DAT from chronic DAT (AuROC > 0.75). Proteins involved in alpha synuclein deposition were over-represented as classifiers of DAT, and many of these proteins have been implicated in a variety of neurodegenerative diseases. These proteins should be considered potential markers for DAT in California sea lions and should be prioritized for future validation studies as biomarkers.
期刊介绍:
Journal of Proteome Research publishes content encompassing all aspects of global protein analysis and function, including the dynamic aspects of genomics, spatio-temporal proteomics, metabonomics and metabolomics, clinical and agricultural proteomics, as well as advances in methodology including bioinformatics. The theme and emphasis is on a multidisciplinary approach to the life sciences through the synergy between the different types of "omics".