SKP-450 inhibits migration and DNA synthesis stimulated by oxidized low density lipoprotein in smooth muscle cells.
This study was carried out to examine the inhibitory effects of SKP-450 (2-[2"(1", 3"-dioxolone)-2-methyl]-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H-1-be nzo pyran), a potassium channel opener, on the proliferation and migration stimulated by oxidized low density lipoprotein (LDL) of cultured smooth muscle cells of Wistar Kyoto rat aorta. SKP-450 (10(-7) and 10(-6) M) as well as probucol (10(-7)-10(-5) M) reduced the production of thiobarbituric acid reactive substances from LDL submitted to CuSO(4) (10 microM). The increased [3H]thymidine incorporation and migration (chemotactic and wound-edge) of the cultured smooth muscle cells in association with increased production of platelet-derived growth factor (PDGF)-BB-like immunoreactivity stimulated by oxidized LDL were significantly reduced by SKP-450 (10(-7)-10(-6) M). Inhibition by SKP-450 of the oxidized LDL-stimulated [3H]thymidine incorporation was antagonized by iberiotoxin (10(-7) M), but not by glibenclamide (10(-6) M), suggestive of mediation of Ca(2+)-activated K(+) channel opening in the action of SKP-450. Taken together, SKP-450 inhibited the proliferation and migration of the smooth muscle cells as well as PDGF production stimulated by oxidized LDL, accompanying with its antiperoxidative action.
Kim
H H
HH
Department of Pharmacology, College of Medicine, Pusan National University, Pusan, South Korea.
Yoo
S E
SE
Lee
W S
WS
Rhim
B Y
BY
Hong
K W
KW
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D000077214:Becaplermin; D001578:Benzopyrans / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D019327:Copper Sulfate / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000819:agonists / Q000187:drug effects*; D020574:Proto-Oncogene Proteins c-sis; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism*
D001578:Benzopyrans; D008077:Lipoproteins, LDL; D010982:Platelet-Derived Growth Factor; D015221:Potassium Channels; D020574:Proto-Oncogene Proteins c-sis; D011760:Pyrrolidinones; D017392:Thiobarbituric Acid Reactive Substances; D000077214:Becaplermin; C096762:KR 30450; D004247:DNA; D019327:Copper Sulfate