Species-dependent effects of the phenolic herbicide ioxynil with potential thyroid hormone disrupting activity: modulation of its cellular uptake and activity by interaction with serum thyroid hormone-binding proteins.
Ioxynil, a phenolic herbicide, is known to exert thyroid hormone (TH) disrupting activity by interfering with TH-binding to plasma proteins and a step of the cellular TH-signaling pathway in restricted animal species. However, comparative studies are still lacking on the TH disruption. We investigated the interaction of [125I]ioxynil with serum proteins from rainbow trout, bullfrog, chicken, pig, rat, and mouse, using native polyacrylamide gel electrophoresis. Candidate ioxynil-binding proteins, which included lipoproteins, albumin and transthyretin (TTR), differed among the vertebrates tested. Rainbow trout and bullfrog tadpole serum had the lowest binding activity for ioxynil, whereas the eutherian serum had the highest binding activity. The cellular uptake of, and response to, ioxynil were suppressed by rat serum greater than by tadpole serum. The cellular uptake of [125I]ioxynil competed strongly with phenols with a single ring, but not with THs. Our results suggested that ioxynil interferes with TH homeostasis in plasma and with a step of cellular TH-signaling pathway other than TH-uptake system, in a species-specific manner.
Department of Biological Science, Faculty of Science, Shizuoka University, Shizuoka 422-8529, Japan.
Sakura
S
Akiyoshi
Gobun
G
Sai
Kiyoshi
K
Yamauchi
D000818:Animals; D002352:Carrier Proteins / Q000097:blood*; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004784:Environmental Monitoring; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000633:toxicity; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D009570:Nitriles / Q000633:toxicity*; D010636:Phenols / Q000633:toxicity*; D011485:Protein Binding / Q000187:drug effects; D011995:Recombination, Genetic / Q000235:genetics; D013045:Species Specificity; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism*; D014284:Triiodothyronine / Q000037:antagonists & inhibitors / Q000378:metabolism; D014982:Xenopus laevis; D000097810:Thyroid Hormone-Binding Proteins
D002352:Carrier Proteins; D006540:Herbicides; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008565:Membrane Proteins; D009570:Nitriles; D010636:Phenols; D013963:Thyroid Hormones; D014284:Triiodothyronine; D000097810:Thyroid Hormone-Binding Proteins; C008161:ioxynil