Solosky Amie M, Claudio Iliana M, Chappel Jessie R, Kirkwood-Donelson Kaylie I, Janech Michael G, Bland Alison M, Gulland Frances M D, Neely Benjamin A, Baker Erin S
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, United States.
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States.
J Proteome Res. 2024 Dec 6;23(12):5577-5585. doi: 10.1021/acs.jproteome.4c00820. Epub 2024 Nov 24.
Domoic acid is a neurotoxin secreted by the marine diatom genus during toxic algal bloom events. California sea lions () are exposed to domoic acid through the ingestion of fish that feed on toxic diatoms, resulting in domoic acid toxicosis (DAT), which can vary from mild to fatal. Sea lions with mild disease can be treated if toxicosis is detected early after exposure. Therefore, rapid diagnosis of DAT is essential but also challenging. In this work, we performed multiomics analyses, specifically proteomic and lipidomic, on blood samples from 31 California sea lions. Fourteen sea lions were diagnosed with DAT based on clinical signs and post-mortem histological examination of brain tissue, and 17 had no evidence of DAT. Proteomic analyses revealed 31 statistically significant proteins in the DAT individuals compared to the non-DAT individuals (adjusted < 0.05). Of these proteins, 19 were decreased in the DAT group of which three were apolipoproteins that are known to transport lipids in the blood, prompting lipidomic analyses. In the lipidomic analyses, 331 lipid species were detected with high confidence and multidimensional separations, and 29 were found to be statistically significant (adjusted < 0.05 and log2(FC) < -1 or >1) in the DAT versus non-DAT comparison. Of these, 28 were lower in the DAT individuals, while only 1 was higher. Furthermore, 15 of the 28 lower concentration lipids were triglycerides, illustrating their putative connection with the perturbed apolipoproteins and potential use in rapid DAT diagnoses.
软骨藻酸是一种在有毒藻华事件期间由海洋硅藻属分泌的神经毒素。加利福尼亚海狮（Zalophus californianus）通过摄食以有毒硅藻为食的鱼类而接触软骨藻酸，导致软骨藻酸中毒（DAT），其严重程度可从轻度到致命。如果在接触后早期发现中毒，患有轻度疾病的海狮可以得到治疗。因此，快速诊断DAT至关重要但也具有挑战性。在这项工作中，我们对31只加利福尼亚海狮的血液样本进行了多组学分析，特别是蛋白质组学和脂质组学分析。根据临床症状和脑组织的死后组织学检查，14只海狮被诊断为患有DAT，17只没有DAT的证据。蛋白质组学分析显示，与非DAT个体相比，DAT个体中有31种具有统计学意义的蛋白质（校正P<0.05）。在这些蛋白质中，有19种在DAT组中减少，其中三种是已知在血液中运输脂质的载脂蛋白，这促使我们进行脂质组学分析。在脂质组学分析中，通过高可信度和多维分离检测到331种脂质种类，在DAT与非DAT的比较中，发现29种具有统计学意义（校正P<0.05且log2（FC）<-1或>1）。其中，28种在DAT个体中含量较低，只有1种较高。此外，28种低浓度脂质中有15种是甘油三酯，说明了它们与受干扰的载脂蛋白的推定联系以及在快速DAT诊断中的潜在用途。
