Biphasic modulation of protein kinase C (PKC) activity by polychlorinated dibenzo-p-dioxins (PCDDs) in serum-deprived rat aortic smooth muscle cells.
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)
Weber
T J
TJ
Department of Veterinary Physiology and Pharmacology, Texas A & M University, College Station 77843-4466.
Ou
X
X
Merchant
M
M
Wang
X
X
Safe
S H
SH
Ramos
K S
KS
D000818:Animals; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D016895:Culture Media, Serum-Free; D003600:Cytosol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013329:Structure-Activity Relationship
D016895:Culture Media, Serum-Free; D006657:Histones; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011493:Protein Kinase C