Aryl hydrocarbon receptor function in early vertebrates: inducibility of cytochrome P450 1A in agnathan and elasmobranch fish

摘要: The mammalian aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that controls the expression of cytochrome P450 1A (CYP1A) genes in response to halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). natural ligand and normal physiologic function this protein are yet unknown. One approach understanding AHR significance determine evolutionary history processes CYP1A induction controlled by mammals. In these studies, was evaluated representative cartilaginous fish (little skate, Raja erinacea) jawless (sea lamprey, Petromyzon marinus Atlantic hagfish, Myxine glutinosa), using model AHR-dependent response. Treatment skate with beta-naphthoflavone (BNF) caused an 8-fold increase hepatic ethoxyresorufin O-deethylase (EROD) activity well 37-fold content immunodetectable protein. Evidence inducibility also obtained for another fish, smooth dogfish Mustelus canis. contrast, EROD not detected untreated lamprey nor treated 3,3'4,4'-tetrachlorobiphenyl (TCB), potent agonist teleosts. A possible homolog microsomes one three antibodies teleost CYP1A, but altered TCB treatment. catalytic were measurable neither induced after treatment TCB. These results suggest AHR-CYP1A signal transduction pathway highly conserved gnathostomes, there may be fundamental differences signaling or coupling agnathan fish. Agnathan hagfish interesting species examining ancestral functions related regulation.