Cytochrome P4501A is induced in endothelial cell lines from the kidney and lung of the bottlenose dolphin, Tursiops truncatus
Cytochrome P4501A is induced in endothelial cell lines from the kidney and lung of the bottlenose dolphin, Tursiops truncatus
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DOI：
10.1016/j.aquatox.2005.10.005
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发表时间：
2006-03-10
影响因子：
4.5
通讯作者：
Stegeman, JJ
中科院分区：
文献类型：
--
作者：
Garrick, RA;Woodin, BR;Stegeman, JJ
海洋哺乳动物对多环和平面卤代芳香烃（PAH 或 PHAH）的存在做出反应，诱导内皮细胞色素 P4501A1 的表达，并通过芳烃受体 (AHR) 转录因子进行调节。其他动物的生理反应，如水肿和炎症，表明内皮细胞可能因暴露于海洋环境中普遍存在的 AHR 激动剂而受到损害。在其他哺乳动物和鱼类中，暴露于 AHR 激动剂的细胞和分子后果已在培养的内皮细胞中得到阐明。我们培养并表征了鲸类内皮细胞 (EC)，并将其用于诱导研究。从宽吻海豚 (Tursiops truncates) 的肺和肾中培养内皮细胞，并将其暴露于 AHR 激动剂 β-萘黄酮 (β NF) 和 2,3,7,8-四氯二苯并-对二恶英 (TCDD)。 beta NF (1-3 mu M) 诱导肺和肾 EC 中 CYP1A1（7-乙氧基试卤灵 O-脱乙基化为试卤灵；EROD）活性显着增加，分别达到 3.6 和 0.92 pmol/mg/min。 TCDD 比 β NF 更有效，也更有效。在 3-10 nM TCDD 下，肺和肾 EC 中 CYP1A1 活性的最大诱导量为 10.1 和 15.2 pmol/mg/min。差异反应表明培养的肺和肾内皮细胞保留了以选择性方式对特定刺激做出反应的能力。毒物暴露的诱导分子机制和生理后果（特别是在脉管系统中）都可以在该系统中进行研究。 (C) 2005 Elsevier B.V. 保留所有权利。
Marine mammals respond to the presence of polycyclic and planar halogenated aromatic hydrocarbons (PAH or PHAH) with the induced expression in endothelium of cytochrome P4501A1, regulated through the aryl hydrocarbon receptor (AHR) transcription factor. Physiological responses in other animals, such as edema and inflammation indicate that the endothelium may be compromised by exposure to AHR agonists, which are ubiquitous in the marine environment. In other mammals and fish the cellular and molecular consequences of exposure to AHR agonists have been elucidated in cultured endothelial cells. We have cultured and characterized cetacean endothelial cells (EC) and used them in induction studies. Endothelial cells were cultured from the lung and kidney of the bottlenose dolphin, Tursiops truncates, and exposed to the AHR agonists beta-naphthoflavone (beta NF) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). beta NF (1-3 mu M) induced significant increases in CYP1A1 (O-deethylation of 7-ethoxyresorufin to resorufin; EROD) activity to 3.6 and 0.92 pmol/mg/min in lung and kidney EC, respectively. TCDD was more potent than beta NF, and more efficacious. with maximum induction of CYP1A1 activity of 10.1 and 15.2 pmol/mg/min in lung and kidney EC at 3-10 nM TCDD. The differential response indicates that the lung and kidney endothelial cells in culture retain the ability to respond in a selective manner to specific stimuli. Both the molecular mechanisms of induction and the physiological consequences, especially in the vasculature, of toxicant exposure can be studied in this system. (C) 2005 Elsevier B.V. All rights reserved.