Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Gujarat 390 002, India.
Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.
Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Apr;1866(4):158889. doi: 10.1016/j.bbalip.2021.158889. Epub 2021 Jan 15.
Temporal expression patterns and activity of two cyclooxygenase (COX-1 and COX-2) isoforms were analysed during early chick embryogenesis to evaluate their roles in development. COX-2 inhibition with etoricoxib resulted in significant structural anomalies such as anophthalmia (born without one or both eyes), phocomelia (underdeveloped or truncated limbs), and gastroschisis (an opening in the abdominal wall), indicating its significance in embryogenesis. Furthermore, the levels of PGE, PGD, PGF, and TXB were assessed using quantitative LC-MS/MS to identify which effector prostanoid (s) had their synthesis initiated by COX-2. COX-2 inhibition was only shown to reduce the level of PGE significantly and hence it could be inferred that the later could be largely under the regulation of activated COX-2 in chick embryos. The compensatory increase in the activity of COX-1 observed in the etoricoxib-treated group helped to maintain the levels of PGD, PGF, and TXB. Though the roles of these three prostanoids in embryogenesis need to be further clarified, it appears that their contribution to the observed developmental anomalies is minimal. This study has shown that COX-2 is functionally active during chick embryogenesis, and it plays a central role in the structural configuration of several organs and tissues through its downstream effector molecule PGE.
在鸡胚早期发育过程中分析了两种环氧化酶(COX-1 和 COX-2)同工型的时间表达模式和活性,以评估它们在发育中的作用。使用依托考昔抑制 COX-2 会导致明显的结构异常,如无眼症(出生时没有一只或两只眼睛)、海豹肢畸形(肢体发育不良或截断)和腹裂(腹壁开口),表明其在胚胎发生中的重要性。此外,还使用定量 LC-MS/MS 评估了 PGE、PGD、PGF 和 TXB 的水平,以确定哪种效应性前列腺素(s)由 COX-2 启动其合成。仅显示 COX-2 抑制可显著降低 PGE 的水平,因此可以推断,鸡胚中激活的 COX-2 可能在很大程度上调节后者。在依托考昔处理组中观察到 COX-1 活性的代偿性增加有助于维持 PGD、PGF 和 TXB 的水平。尽管这三种前列腺素在胚胎发生中的作用需要进一步阐明,但它们对观察到的发育异常的贡献似乎很小。这项研究表明,COX-2 在鸡胚发生过程中具有功能活性,并且通过其下游效应分子 PGE 在几个器官和组织的结构配置中发挥核心作用。