School of Life Sciences, The Chinese University of Hong Kong, Sha Tin, N.T., Hong Kong Special Administrative Region, China.
Metallomics. 2014 May;6(5):1057-67. doi: 10.1039/c3mt00366c.
Zebrafish (Danio rerio) is a freshwater fish species of Cyprinidae known for its copper (Cu) intolerance, yet the underlying mechanisms of the sensitivity remain unclear. In this study, we examined the highly conserved molecular machineries in the copper handling system, namely ATOX1, ATP7A, ATP7B, and CTR1, by profiling their gene expression patterns among tissues before and after acute waterborne Cu exposure, and investigating their intracellular localization patterns using a zebrafish hepatocyte cell line, ZFL. We found that ATP7B was weak in its response toward Cu exposure to elicit its copper efflux function. Tissue distribution of these Cu transporters, however, revealed a distinct expression profile compared with mammals and other fish, particularly ATP7A, which unlike ATP7B was highly expressed in the liver, while ATP7B, not ATP7A, was specifically expressed in the intestine. ATOX1 transcript expression was also found to be significantly up-regulated with acute waterborne Cu, in contrast to the decreased expression found in other fish. A possible explanation for the Cu sensitivity in zebrafish is discussed.
斑马鱼（Danio rerio）是一种淡水鱼类，属于鲤科，以对铜（Cu）不耐受而闻名，但敏感的潜在机制仍不清楚。在这项研究中，我们通过研究急性水暴露前后组织中铜处理系统中高度保守的分子机制，即 ATOX1、ATP7A、ATP7B 和 CTR1，研究了它们的基因表达模式，并使用斑马鱼肝细胞系 ZFL 研究了它们的细胞内定位模式。我们发现，ATP7B 对 Cu 暴露的反应较弱，无法发挥其铜外排功能。然而，这些 Cu 转运蛋白的组织分布与哺乳动物和其他鱼类有明显不同的表达模式，特别是 ATP7A，它在肝脏中的表达水平高于 ATP7B，而 ATP7B 而非 ATP7A 则在肠道中特异性表达。我们还发现，与其他鱼类的表达水平下降不同，急性水暴露后 ATOX1 的转录表达显著上调。我们讨论了斑马鱼对 Cu 敏感的可能解释。
