Characterization and comparison of transcriptional activities of the retinoid X receptors by various organotin compounds in three prosobranch gastropods; Thais clavigera, Nucella lapillus and Babylonia japonica

• Published in: Aquatic toxicology 2018-06, Vol.199, p.103-115
• Main Authors: Urushitani, Hiroshi, Katsu, Yoshinao, Kagechika, Hiroyuki, Sousa, Ana C.A., Barroso, Carlos M., Ohta, Yasuhiko, Shiraishi, Hiroaki, Iguchi, Taisen, Horiguchi, Toshihiro
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Babylonia japonica; Female; Gastropoda - drug effects; Gastropoda - metabolism; Imposex; Nucella lapillus; Organotin Compounds - toxicity; Organotins; Protein Isoforms - genetics; Protein Isoforms - metabolism; Retinoid X receptor (RXR); Retinoid X Receptors - genetics; Retinoid X Receptors - metabolism; Retinoids - pharmacology; Sequence Alignment; Thais clavigera; Transcription, Genetic - drug effects; Trialkyltin Compounds - toxicity; Water Pollutants, Chemical - toxicity
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2018.03.029

•Two cDNAs of RXR were newly isolated from the ivory shell, Babylonia japonica.•Transcriptional activities of molluscan RXR isoforms were induced by RXR agonists.•Transcriptional activities of molluscan RXRs were inhibited by RXR antagonist.•Transcriptional activities of RXRs changed when response elements changed.•The gastropod RXR isoforms might control the transcription of different genes. Two cDNAs of RXR were isolated, for the first time, from the ivory shell, Babylonia japonica, and the transcriptional activities were tested in vitro to compare with other gastropod (Thais clavigera and Nucella lapillus) RXR isoforms. The transcriptional activities of all of these RXR isoforms were significantly induced by mammalian RXR agonist, 9-cis retinoic acid (9cRA). The transcriptional activity of T. clavigera RXR-1 was also examined by using 9cRA and 16 organotin compounds, and significant ligand-dependent transactivations were observed by 9cRA and 5 organotins (tributyltin (TBT), tetrabutyltin (TeBT), tripropyltin (TPrT), tricyclohexyltin (TcHT) and triphenyltin (TPhT)). These 5 organotins also induced significant transcriptional activities in N. lapillus and B. japonica RXR isoforms. These 4 organotins, except for TeBT, have been reported to promote the development of imposex after a month of a single injection each, using female T. clavigera. To investigate the function of gastropod RXR isoforms, the effects of mammalian specific pan-agonist, PA024, and pan-antagonist, HX531, were examined, and significant induction of transcriptional activity by PA024 was demonstrated in these gastropod RXR isoforms. The additions of HX531 significantly suppressed the transcriptional activities of these gastropod RXR isoforms by 9cRA and 5 organotins. Using the mammalian two retinoic acid response elements, the transcriptional activities by 2 agonists, 9cRA and PA024, were different among the RXR isoforms of each gastropod species. With retinoid X response element (RXRE), transcriptional activities of TcRXR-1, BjRXR-1, and NlRXRa were significantly higher than those of TcRXR-2, BjRXR-2, and NlRXRb. Transcriptional activities of TcRXR-2, BjRXR-2, and NlRXRb, however, were significantly higher than those of TcRXR-1, BjRXR-1, and NlRXRa with thyroid hormone response element, TREpal. Thus, induction of imposex in prosobranch gastropods is strongly suggested to be triggered by 9cRA and certain organotins, such as TBT and TPhT through the activation of RXRs. These gastropod RXRs