title: Tributyltin-sulfhydryl interaction as a cause of immunotoxicity in phagocytes of tunicates.
abstract: We reported elsewhere that tributyltin (TBT) has detrimental effects on the immune system of the colonial ascidian Botryllus schlosseri, through interaction with calmodulin and alteration of Ca2+ homeostasis. Here, we studied the capability of TBT to react with intracellular thiols. After exposure to 0.1 microM TBT, a significant decrease in B. schlosseri hemocytes stained for total thiols and reduced glutathione (GSH) was detected. Exogenous sulfhydryl and sulfide compounds can prevent TBT-induced cell morphology alterations and decrease the percentage of tin-containing hemocytes, indicating the scavenging ability of thiol peptides. No effects were observed with disulfides, N-acetylcysteine, or the GSH fragment Cys-Gly. No interactions were observed with TBT and carmustine, whereas TBT and N-ethylmaleimide (NEM) showed a combined antagonistic action, suggesting direct interaction of TBT with thiol-containing compounds. Regulation of Ca2+ efflux from internal stores seems to depend on stimulation of the inositol 1,4,5-trisphosphate (InsP3) receptor by oxidized glutathione (GSSG), which results from interactions of both TBT-GSH and TBT-GSH reductase.
authors.affiliation: Department of Biology, University of Padova, Via Ugo Bassi 58/B, Padova 35131, Italy. ascilab@civ.bio.unipd.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Cima
authors.forename: Loriano
authors.initials: L
authors.lastname: Ballarin
mesh_terms: D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D006434:Hemocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000633:toxicity*; D010586:Phagocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000032:analysis / Q000494:pharmacology*; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014561:Urochordata / Q000276:immunology / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015262:Xenobiotics / Q000633:toxicity*
chemical_list: D007166:Immunosuppressive Agents; D013438:Sulfhydryl Compounds; D014220:Trialkyltin Compounds; D014874:Water Pollutants, Chemical; D015262:Xenobiotics; C011559:tributyltin; D005978:Glutathione; D002118:Calcium