Polyamine-induced changes in the sedimentation profile and DNA binding of aryl hydrocarbon receptor.
Aryl hydrocarbon (Ah) receptor mediates the toxic action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We studied the effects of polyamines--putrescine, spermidine and spermine--on the physical chemical properties of Ah receptor from A431 cells. Spermidine and spermine caused the precipitation of 9S oligomeric receptor with a gradual decrease in the receptor peak during density gradient sedimentation. RNase A treatment transformed the 9S Ah receptor to a 6S form and DNA binding increased by 2-fold. Following partial purification of transformed Ah receptor by preparative sucrose gradient centrifugation, it lost the ability to bind to DNA, but addition of spermidine increased DNA binding in a concentration-dependent manner. These data show that polyamines modulate the structure and DNA binding of Ah receptor and suggest that cellular polyamine levels might be important in the tissue specific toxicity of TCDD.
Thomas
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Department of Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway 08854.
Gallo
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MA
D001665:Binding Sites / Q000187:drug effects; D002499:Centrifugation, Density Gradient; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D011073:Polyamines / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011700:Putrescine / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011073:Polyamines; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D013096:Spermine; D004247:DNA; D012260:Ribonucleases; D013095:Spermidine; D011700:Putrescine