Weber T J, Ou X, Merchant M, Wang X, Safe S H, Ramos K S
Department of Veterinary Physiology and Pharmacology, Texas A & M University, College Station 77843-4466.
J Biochem Toxicol. 1994 Jun;9(3):113-20. doi: 10.1002/jbt.2570090302.
Previous studies in this laboratory have shown that benzo(a)pyrene (BaP) modulates protein kinase C (PKC)-mediated phosphorylation of aortic smooth muscle cell (SMC) proteins. This observation is consistent with the ability of other aromatic hydrocarbons (AHs), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), to modulate kinase activities in cells of hepatic, testicular, and thymic origin. Because all these chemicals share the ability to bind the aryl hydrocarbon receptor (AhR), the present studies were conducted to determine if changes in PKC activity by AHs conform with established structure-activity relationships. Experiments were conducted to examine the effects of TCDD, 2,3,7,8-tetrachlorodibenzofuran (TCDF), and 2,8-dichlorodibenzodioxin (DCDD) on the phosphorylation of exogenous histone type-III under basal and PKC-activating conditions. These congeners exhibit both high (TCDD and TCDF) and low (DCDD) AhR agonist activities. Measurements of kinase activity were conducted in the cytosolic and particulate fractions of growth-arrested (i.e., serum-deprived) cultured rat aortic SMCs incubated with 10 nM TCDD, TCDF, and DCDD for 0.5, 12, or 24 hours. No changes in basal kinase activity were induced by these chemicals at any of the times tested. Significant decreases in cytosolic and particulate PKC activity relative to controls were observed upon exposure of SMCs for 0.5 hours to 10 nM TCDD, TCDF, and DCDD. In contrast, SMCs exposed to TCDD and TCDF for 12 hours exhibited a significant increase in PKC activity in both cytosolic and particulate fractions. The PKC activity in cells exposed to DCDD for 12 hours was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
本实验室之前的研究表明，苯并(a)芘（BaP）可调节蛋白激酶C（PKC）介导的主动脉平滑肌细胞（SMC）蛋白磷酸化。这一观察结果与其他芳烃（AHs），如2,3,7,8-四氯二苯并对二恶英（TCDD），调节肝、睾丸和胸腺来源细胞中激酶活性的能力一致。由于所有这些化学物质都具有结合芳烃受体（AhR）的能力，因此进行了本研究以确定AHs引起的PKC活性变化是否符合已确立的构效关系。进行实验以检查TCDD、2,3,7,8-四氯二苯并呋喃（TCDF）和2,8-二氯二苯并二恶英（DCDD）在基础条件和PKC激活条件下对外源组蛋白III型磷酸化的影响。这些同系物表现出高（TCDD和TCDF）和低（DCDD）AhR激动剂活性。在生长停滞（即血清剥夺）的培养大鼠主动脉SMC的胞质和颗粒部分中进行激酶活性测量，这些细胞与10 nM TCDD、TCDF和DCDD孵育0.5、12或24小时。在任何测试时间，这些化学物质均未诱导基础激酶活性发生变化。将SMC暴露于10 nM TCDD、TCDF和DCDD 0.5小时后，相对于对照组，胞质和颗粒PKC活性显著降低。相比之下，暴露于TCDD和TCDF 12小时的SMC在胞质和颗粒部分的PKC活性均显著增加。暴露于DCDD 12小时的细胞中的PKC活性未改变。（摘要截断于250字）
