Garlic extract methylallyl thiosulfinate blocks insulin potentiation of platelet-derived growth factor-stimulated migration of vascular smooth muscle cells.
Platelet-derived growth factor (PDGF) is a potent inducer of vascular smooth muscle cell (VSMC) migration, whereas insulin, in physiological concentrations, helps maintain the nonproliferative phenotype of these cells. However, hyperinsulinemia (10 nmol/L) significantly potentiates the PDGF (30 pmol/L)-induced migration of VSMC. This potentiating effect of hyperinsulinemia appears to be mediated by increased availability of geranylgeranylated Rho-A. Hyperinsulinemia significantly increased the activity of geranylgeranyltransferase I (GGTase I) and the amounts of prenylated Rho-A. This action of hyperinsulinemia was inhibited by methylallyl thiosulfinate (MAT), a component of garlic extract, which exerted a strong anti-GGTase I activity. MAT also completely inhibited the ability of hyperinsulinemia to potentiate the PDGF-induced VSMC migration. Thus, the purported anti-atherogenic action of garlic may be related to its inhibitory influence on GGTase I.
Golovchenko
Inga
I
Research Service of the Veterans Affairs Medical Center, Denver, CO 80220, USA.
Yang
Chul-Hak
CH
Goalstone
Marc L
ML
Draznin
Boris
B
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005737:Garlic / Q000737:chemistry*; D007328:Insulin / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology*; D010936:Plant Extracts / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D013441:Sulfinic Acids / Q000494:pharmacology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D004791:Enzyme Inhibitors; D007328:Insulin; D010936:Plant Extracts; D010982:Platelet-Derived Growth Factor; D013441:Sulfinic Acids; C471935:methylallyl thiosulfinate; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D020742:rhoA GTP-Binding Protein