University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, 389 25, Vodnany, Czech Republic; Swedish University of Agricultural Sciences, Department of Molecular Sciences, P.O. Box 7015, SE-750 07, Uppsala, Sweden.
University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, 389 25, Vodnany, Czech Republic; Swedish University of Agricultural Sciences, Department of Molecular Sciences, P.O. Box 7015, SE-750 07, Uppsala, Sweden.
Toxicol Lett. 2021 May 1;341:1-10. doi: 10.1016/j.toxlet.2021.01.011. Epub 2021 Jan 8.
Piscine cytochrome P450 (CYP) enzymes play an important role in the metabolism of xenobiotics. Xenobiotics often act as inducers of CYP1A1 and CYP3A expression and activity in fish. We compared constitutive mRNA expression of CYP1A1, CYP3A27, and CYP3A45 and catalytic activity of CYP1A (7-ethoxyresorufin-O-deethylation, EROD) and CYP3A-like (benzyloxy-4-trifluoromethylcoumarin-O-debenzyloxylation, BFCOD) enzymes in the following six rainbow trout tissues: liver, gill, heart, brain, intestine, and gonad. mRNA expression and activity were present in all investigated tissues. The CYP1A1 mRNA expression was higher in the liver, gill, heart, and brain compared to gonad and intestine. The intestine was the main site of CYP3A27 and CYP3A45 expression. The highest EROD and BFCOD activity was observed in liver tissue followed in descending order by heart, brain, gill, intestine, and gonad. Such differences might be related to the role of CYP physiological functions in the specific tissue. Rainbow trout exposure to 50 mg/kg of β-naphthoflavone for 48 h resulted in a 7.5- and 5.9-fold increase in liver EROD and BFCOD activity, respectively. In vitro EROD activity inhibition with ellipticine showed tissue-specific inhibition, while ketoconazole decreased BFCOD activity by 50-98 % in all tissues. Further studies are needed to identify all CYP isoforms that are responsible for these activities and modes of regulation.
鱼类细胞色素 P450（CYP）酶在异生物质代谢中起着重要作用。异生物质通常作为鱼类 CYP1A1 和 CYP3A 表达和活性的诱导剂。我们比较了以下六种虹鳟鱼组织中 CYP1A1、CYP3A27 和 CYP3A45 的组成型 mRNA 表达和 CYP1A（7-乙氧基resorufin-O-去乙基化，EROD）和 CYP3A 样（苯甲氧基-4-三氟甲基香豆素-O-去苯甲氧基化，BFCOD）酶的催化活性。所有研究的组织中均存在 mRNA 表达和活性。与性腺和肠相比，肝、鳃、心脏和脑中的 CYP1A1 mRNA 表达较高。CYP3A27 和 CYP3A45 的表达主要在肠中。肝组织中 EROD 和 BFCOD 活性最高，其次依次为心脏、大脑、鳃、肠和性腺。这些差异可能与 CYP 生理功能在特定组织中的作用有关。虹鳟鱼暴露于 50mg/kgβ-萘黄酮 48h 后，肝 EROD 和 BFCOD 活性分别增加了 7.5 倍和 5.9 倍。用椭圆素对 EROD 活性的体外抑制显示出组织特异性抑制，而酮康唑使所有组织中的 BFCOD 活性降低了 50-98%。需要进一步研究以确定负责这些活性和调节方式的所有 CYP 同工酶。
