CCMAR - Centro de Ciências do Mar (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal.
CCMAR - Centro de Ciências do Mar (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal.
Sci Total Environ. 2022 Mar 25;814:152671. doi: 10.1016/j.scitotenv.2021.152671. Epub 2021 Dec 27.
Teleost fish skin-scales are essential for protection and homeostasis and the largest tissue in direct contact with the environment, but their potential as early indicators of pollutant exposure are hampered by limited knowledge about this model. This study evaluated multi-level impacts of in vivo exposure of European sea bass to fluoxetine (FLX, a selective serotonin-reuptake inhibitor and an emerging pollutant) and 17β-estradiol (E2, a natural hormone and representative of diverse estrogenic endocrine-disrupting pollutants). Exposed fish had significantly increased circulating levels of FLX and its active metabolite nor-FLX that, in contrast to E2, did not have estrogenic effects on most fish plasma and scale indicators. Quantitative proteomics using SWATH-MS identified 985 proteins in the scale total proteome. 213 proteins were significantly modified 5 days after exposure to E2 or FLX and 31 were common to both treatments and responded in the same way. Common biological processes significantly affected by both treatments were protein turnover and cytoskeleton reorganization. E2 specifically up-regulated proteins related to protein production and degradation and down-regulated the cytoskeleton/extracellular matrix and innate immune proteins. FLX caused both up- and down-regulation of protein synthesis and energy metabolism. Multiple estrogen and serotonin receptor and transporter transcripts were altered in sea bass scales after E2 and/or FLX exposure, revealing complex disruptive effects in estrogen/serotonin responsiveness, which may account for the partially overlapping effects of E2 and FLX on the proteome. A large number (103) of FLX-specifically regulated proteins indicated numerous actions independent of estrogen signalling. This study provides the first quantitative proteome of the fish skin-scale barrier, elucidates routes of action and biochemical and molecular signatures of E2 or FLX-exposure and identifies potential physiological consequences and candidate biomarkers of pollutant exposure, for monitoring and risk assessment.
硬骨鱼的皮肤鳞片对于保护和体内平衡至关重要，是与环境直接接触的最大组织，但由于对这种模式的了解有限，它们作为污染物暴露的早期指标的潜力受到了阻碍。本研究评估了在体暴露于氟西汀（FLX，一种选择性 5-羟色胺再摄取抑制剂和新兴污染物）和 17β-雌二醇（E2，一种天然激素和各种雌激素内分泌干扰污染物的代表）对欧洲鲈鱼的多水平影响。暴露于氟西汀的鱼的循环水平显著升高，其活性代谢物 nor-FLX 与 E2 相反，对大多数鱼血浆和鳞片指标没有雌激素作用。使用 SWATH-MS 的定量蛋白质组学在鳞片总蛋白质组中鉴定出 985 种蛋白质。暴露于 E2 或 FLX 5 天后，有 213 种蛋白质显著改变，其中 31 种蛋白质为两种处理所共有，且以相同方式响应。受两种处理显著影响的共同生物学过程是蛋白质周转和细胞骨架重组。E2 特异性地上调与蛋白质产生和降解相关的蛋白质，并下调细胞骨架/细胞外基质和先天免疫蛋白。FLX 引起蛋白质合成和能量代谢的上调和下调。E2 和/或 FLX 暴露后，鲈鱼鳞片中的多种雌激素和 5-羟色胺受体和转运蛋白转录本发生改变，揭示了雌激素/5-羟色胺反应性的复杂破坏作用，这可能解释了 E2 和 FLX 对蛋白质组的部分重叠作用。大量（103 种）FLX 特异性调节的蛋白质表明存在许多独立于雌激素信号的作用。本研究提供了鱼类皮肤鳞片屏障的第一个定量蛋白质组学，阐明了 E2 或 FLX 暴露的作用途径以及生化和分子特征，并确定了污染物暴露的潜在生理后果和候选生物标志物，用于监测和风险评估。
