Nechat Sumi, Shadi Melina, Schreier Andrea D, Fangue Nann A, Sundberg John P, Rice Robert H
Department of Environmental Toxicology, University of California, Davis, CA, 95616, USA.
Department of Animal Science, University of California, Davis, CA, 95616, USA.
Sci Rep. 2025 Jul 24;15(1):26875. doi: 10.1038/s41598-025-12299-7.
Sturgeon species are threatened or endangered worldwide due to habitat loss and increasing pollution. An epithelial cell culture model promises to help investigate hazardous environmental exposures. Stratified squamous integument of green and white sturgeons (Acipenser medirostris and transmontanus, respectively) and cells cultured from their epithelia expressed substantial levels of TGM1-like transglutaminases, types I and II keratins and aryl hydrocarbon receptor (AHR) proteins analogous to those in mammalian integument. Epithelial cells cultured from the rim of the mouth, oral cavity and ampullae of Lorenzini exhibited dramatic growth suppression upon exposure to environmentally relevant levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a model compound for ubiquitous environmental combustion products that activate the AHR. The rho kinase inhibitor Y27632 markedly increased cell growth in culture and, surprisingly, prevented growth suppression by TCDD. Thus, these epithelial cell cultures provide an intriguing model for studying the mechanism by which activation of the AHR produces adverse effects. Evidently, contributions from genome duplication, gene duplication, gene loss and complications of polyploidization have endowed sturgeon with multiple forms of AHR, in this case 3 pairs of closely related genes. AHR1 and AHR2 are predicted to bind TCDD with high affinity, which could help rationalize the cellular sensitivity to AHR activation.
由于栖息地丧失和污染加剧，鲟鱼物种在全球范围内受到威胁或濒临灭绝。上皮细胞培养模型有望有助于研究有害的环境暴露。绿鲟和白鲟（分别为中吻鲟和高首鲟）的分层鳞状外皮及其上皮细胞培养物表达了大量类似于哺乳动物外皮中的转谷氨酰胺酶1样转谷氨酰胺酶、I型和II型角蛋白以及芳烃受体（AHR）蛋白。从口缘、口腔和罗伦氏壶腹培养的上皮细胞在暴露于与环境相关水平的2,3,7,8-四氯二苯并对二恶英（TCDD）时表现出显著的生长抑制，TCDD是一种能激活AHR的普遍存在的环境燃烧产物的模型化合物。Rho激酶抑制剂Y27632显著增加了培养物中的细胞生长，令人惊讶的是，它还能防止TCDD对生长的抑制。因此，这些上皮细胞培养物为研究AHR激活产生不良反应的机制提供了一个有趣的模型。显然，基因组复制、基因复制、基因丢失和多倍体化的复杂性赋予了鲟鱼多种形式的AHR，在这种情况下是3对密切相关的基因。预计AHR1和AHR2与TCDD具有高亲和力结合，这有助于解释细胞对AHR激活的敏感性。
