Thomas T, Gallo M A
Department of Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway 08854.
Toxicol Lett. 1994 Oct;74(1):35-49. doi: 10.1016/0378-4274(94)90072-8.
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.
芳基烃(Ah)受体介导2,3,7,8-四氯二苯并对二恶英(TCDD)的毒性作用。我们研究了多胺——腐胺、亚精胺和精胺——对A431细胞中Ah受体物理化学性质的影响。亚精胺和精胺导致9S寡聚体受体沉淀,在密度梯度沉降过程中受体峰逐渐降低。核糖核酸酶A处理将9S Ah受体转化为6S形式,DNA结合增加了2倍。通过制备性蔗糖梯度离心对转化后的Ah受体进行部分纯化后,它失去了与DNA结合的能力,但添加亚精胺以浓度依赖的方式增加了DNA结合。这些数据表明多胺调节Ah受体的结构和DNA结合,并表明细胞内多胺水平可能在TCDD的组织特异性毒性中起重要作用。