Marine Biology Research Division, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA; Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
Marine Biology Research Division, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA.
Aquat Toxicol. 2019 Jul;212:88-97. doi: 10.1016/j.aquatox.2019.04.013. Epub 2019 Apr 25.
Ionocytes are specialized cells in the epidermis of embryonic zebrafish (Danio rerio) that play important roles in ion homeostasis and have functional similarities to mammalian renal cells. Here, we examined whether these cells might also share another functional similarity with renal cells, which is the presence of efflux transporter activities useful for elimination of toxic small molecules. Xenobiotic transporters (XTs), including the ATP-Binding Cassette (ABC) family, are a major defense mechanism against diffusible toxic molecules in aquatic embryos, including zebrafish, but their activity in the ionocytes has not previously been studied. Using fluorescent small molecule substrates of XT, we observed that specific populations of ionocytes uptake and efflux fluorescent small molecules in a manner consistent with active transport. We specifically identified a P-gp/ABCB1 inhibitor-sensitive efflux activity in the H-ATPase-rich (HR) ionocytes, and show that these cells exhibit enriched expression of the ABCB gene, abcb5. The results extend our understanding of the functional significance of zebrafish ionocytes and indicate that these cells could play an important role in protection of the fish embryo from harmful small molecules.
离子细胞是胚胎斑马鱼(Danio rerio)表皮中的特化细胞,在离子稳态中发挥重要作用,并且与哺乳动物肾脏细胞具有功能相似性。在这里,我们研究了这些细胞是否可能与肾脏细胞具有另一个功能相似性,即存在有助于排出有毒小分子的外排转运体活性。外源性转运体(XTs),包括 ATP 结合盒(ABC)家族,是水生胚胎(包括斑马鱼)中针对可扩散有毒分子的主要防御机制,但它们在离子细胞中的活性尚未得到研究。使用 XT 的荧光小分子底物,我们观察到特定群体的离子细胞以与主动运输一致的方式摄取和外排荧光小分子。我们特别鉴定了 H-ATPase 丰富(HR)离子细胞中 P-糖蛋白/ABCB1 抑制剂敏感的外排活性,并表明这些细胞表现出 ABCB 基因 abcb5 的丰富表达。这些结果扩展了我们对斑马鱼离子细胞功能意义的理解,并表明这些细胞可能在保护鱼类胚胎免受有害小分子侵害方面发挥重要作用。