Inhibitory effect of dehydrozingerone on vascular smooth muscle cell function.
OBJECTIVE
Growth factor and oxidative stress-mediated migration and proliferation of vascular smooth muscle cells (VSMCs) play a key role in the pathogenesis of atherosclerosis. The objective of this study was to assess the ability of dehydrozingerone, a structural analog of curcumin, to inhibit PDGF-stimulated vascular functions in VSMCs.


METHODS
VSMCs isolated from adult rats were treated with dehydrozingerone (0 to 50 microM) before challenge with PDGF (10 ng/mL) and migration, proliferation, and collagen synthesis were assayed by transwell-migration, thymidine-, and L-proline-incorporation assays, respectively. Phosphorylation of PDGF-receptor (PDGFR) and Akt were assessed by Western blotting. Cellular protein tyrosine phosphatase (PTP) activity was determined by the extent of p-nitro-phenyl phosphate hydrolysis.


RESULTS
Dehydrozingerone elicited a concentration-dependent inhibition of PDGF-stimulated VSMC migration, proliferation, collagen synthesis, and PDGF/H2O2-stimulated phosphorylation of PDGFR-beta and downstream Akt. Dehydrozingerone also inhibited H2O2-mediated oxidation of PTP.


CONCLUSIONS
Dehydrozingerone is a potent inhibitor of growth factor/ H2O2-stimulated VSMC functions and may play a critical role in regulating these events after vascular injury. Inhibition of oxidation of cellular phosphatases may represent one of the mechanisms by which dehydrozingerone inhibits these VSMC functions. Inability of the structural analog isoeugenol to inhibit PDGF-signaling suggests that the carbonyl side chain may be necessary for activity.
Liu
Yizhen
Y
Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming, USA.
Dolence
Julia
J
Ren
Jun
J
Rao
Mna
M
Sreejayan
Nair
N
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D003474:Curcumin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D013343:Styrenes / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D013343:Styrenes; C052933:methyl-3-methoxy-4-hydroxystyryl ketone; D003094:Collagen; D020797:Receptor, Platelet-Derived Growth Factor beta; D003474:Curcumin