Developmental expression of functional cyclooxygenases in zebrafish
Developmental expression of functional cyclooxygenases in zebrafish
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DOI：
10.1073/pnas.112217799
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发表时间：
2002-06-11
影响因子：
11.1
通讯作者：
FitzGerald, GA
中科院分区：
文献类型：
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作者：
Grosser, T;Yusuff, S;FitzGerald, GA
由于考克斯-2在小鼠生殖和肾器官形成中的作用，限制了对环加氧酶（CoXs）的研究。我们试图表征考克斯在斑马鱼（z）中的表达和功能。克隆了zCOX-1和zCOX-2的全长cDNA，分别定位于5号和2号染色体的保守区，推导出的蛋白质与人同源性为67%。前列腺素（PG）E-2是质谱法检测到的主要zKOX产物。药理学抑制剂在针对异源表达的zKOX亚型时表现出选择性。斑马鱼血小板体外聚集和体内止血对zCOX-1的抑制敏感，但对zCOX-2不敏感。两种zCOX在发育过程中广泛表达，zCOX-1的敲低导致早期胚胎发生期间的生长停滞。zCOX-1在胚胎血管系统中广泛存在，而zCOX-2表现出更有限的表达模式。两种zCOX同种型在遗传和功能上与其哺乳动物直系同源物同源。斑马鱼为考克斯生物学和发育研究提供了一个易于操作的模型系统。
Study of the cyclooxygenases (CoXs) has been limited by the role of COX-2 in murine reproduction and renal organogenesis. We sought to characterize COX expression and function in zebrafish (z). Full-length cDNAs of zCOX-1 and zCOX-2 were cloned and assigned to conserved regions of chromosomes 5 and 2, respectively, The deduced proteins are 67% homologous with their human orthologs. Prostaglandin (PG) E-2 is the predominant zKOX product detected by mass spectrometry. Pharmacological inhibitors demonstrate selectivity when directed against heterologously expressed zKOX isoforms. Zebrafish thrombocyte aggregation ex vivo and hemostasis in vivo are sensitive to inhibition of zCOX-1, but not zCOX-2. Both zCOXs were widely expressed during development, and knockdown of zCOX-1 causes growth arrest during early embryogenesis. zCOX-1 is widely evident in the embryonic vasculature, whereas zCOX-2 exhibits a more restricted pattern of expression. Both zCOX isoforms are genetically and functionally homologous to their mammalian orthologs. The zebrafish affords a tractable model system for the study of COX biology and development.