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Inhibitory effect of dehydrozingerone on vascular smooth muscle cell function.

AbstractBACKGROUND/AIMS:
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.
AuthorsYizhen Liu, Julia Dolence, Jun Ren, Mna Rao, Nair Sreejayan
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 52 Issue 5 Pg. 422-9 (Nov 2008) ISSN: 1533-4023 [Electronic] United States
PMID19033821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Platelet-Derived Growth Factor
  • Styrenes
  • methyl-3-methoxy-4-hydroxystyryl ketone
  • Collagen
  • Receptor, Platelet-Derived Growth Factor beta
  • Curcumin
Topics
  • Animals
  • Aorta, Thoracic (cytology, drug effects, enzymology, metabolism)
  • Cell Movement (drug effects)
  • Cell Proliferation (drug effects)
  • Cells, Cultured
  • Collagen (biosynthesis)
  • Curcumin (pharmacology)
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Muscle, Smooth, Vascular (cytology, drug effects, enzymology, metabolism)
  • Phosphorylation
  • Platelet-Derived Growth Factor (metabolism, pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Platelet-Derived Growth Factor beta (metabolism)
  • Signal Transduction
  • Styrenes (pharmacology)
  • Tunica Intima (drug effects, enzymology, metabolism)

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