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In this context, the aim of this study was to shed light on the ligand affinity and functions of four NR1J1 paralogs identified in the marine mussel Mytilus galloprovincialis, employing a dual-luciferase reporter assay. To achieve this, the activation patterns of these paralogs in response to various toxins, including freshwater cyanotoxins (Anatoxin-a, Cylindrospermopsin, and Microcystin-LR, -RR, and -YR) and marine algal toxins (Nodularin, Saxitoxin, and Tetrodotoxin), alongside natural compounds (Saint John\u2019s Wort, Ursolic Acid, and 8-Methoxypsoralene) and microalgal extracts (Tetraselmis, Isochrysis, LEGE 95046, and LEGE 91351 extracts), were studied. The investigation revealed nuanced differences in paralog response patterns, highlighting the remarkable sensitivity of MgaNR1J1\u03b3 and MgaNR1J1\u03b4 paralogs to several toxins. In conclusion, this study sheds light on the intricate mechanisms of xenobiotic metabolism and detoxification, particularly focusing on the role of marine mussel NR1J1 in responding to a diverse array of compounds. Furthermore, comparative analysis with human PXR revealed potential species-specific adaptations in detoxification mechanisms, suggesting evolutionary implications. These findings deepen our understanding of PXR-mediated metabolism mechanisms, offering insights into environmental monitoring and evolutionary biology research.<\/jats:p>","DOI":"10.3390\/ijms25126287","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T04:38:56Z","timestamp":1717735136000},"page":"6287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterization of NR1J1 Paralog Responses of Marine Mussels: Insights from Toxins and Natural Activators"],"prefix":"10.3390","volume":"25","author":[{"given":"Antonio","family":"Casas-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor Garc\u00eda Gonz\u00e1lez n\u25e62, 41012 Seville, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6358-3694","authenticated-orcid":false,"given":"Concepci\u00f3n","family":"Medrano-Padial","sequence":"additional","affiliation":[{"name":"Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor Garc\u00eda Gonz\u00e1lez n\u25e62, 41012 Seville, Spain"},{"name":"Laboratorio de Fitoqu\u00edmica y Alimentos Saludables (LabFAS), Centro de Edafolog\u00eda y Biolog\u00eda Aplicada del Segura, Consejo Superior de Investigaciones Cient\u00edficas (CEBAS-CSIC), Campus Universitario 25, Espinardo, 30100 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7546-3294","authenticated-orcid":false,"given":"Angeles","family":"Jos","sequence":"additional","affiliation":[{"name":"Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor Garc\u00eda Gonz\u00e1lez n\u25e62, 41012 Seville, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1524-748X","authenticated-orcid":false,"given":"Ana M.","family":"Came\u00e1n","sequence":"additional","affiliation":[{"name":"Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor Garc\u00eda Gonz\u00e1lez n\u25e62, 41012 Seville, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4621-885X","authenticated-orcid":false,"given":"Alexandre","family":"Campos","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR\/CIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos, s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-2108","authenticated-orcid":false,"given":"Elza","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR\/CIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos, s\/n, 4450-208 Matosinhos, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Laudet, V., and Gronemeyer, H. (2002). The Nuclear Receptor Facts Book, Academic Press. 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