SKP-450 inhibits migration and DNA synthesis stimulated by oxidized low density lipoprotein in smooth muscle cells.

Abstract

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.

• Authors: H H Kim, S E Yoo, W S Lee, B Y Rhim, K W Hong
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 383 Issue 3 Pg. 373-9 (Nov 03 1999) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10594331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzopyrans
• Lipoproteins, LDL
• Platelet-Derived Growth Factor
• Potassium Channels
• Proto-Oncogene Proteins c-sis
• Pyrrolidinones
• Thiobarbituric Acid Reactive Substances
• Becaplermin
• KR 30450
• DNA
• Copper Sulfate

Topics

• Animals
• Aorta (cytology, drug effects)
• Becaplermin
• Benzopyrans (pharmacology)
• Cell Movement (drug effects)
• Cells, Cultured
• Copper Sulfate (pharmacology)
• DNA (biosynthesis, drug effects)
• Lipid Peroxidation (drug effects)
• Lipoproteins, LDL (drug effects, pharmacology)
• Male
• Muscle, Smooth, Vascular (cytology, drug effects)
• Platelet-Derived Growth Factor (drug effects, metabolism)
• Potassium Channels (agonists, drug effects)
• Proto-Oncogene Proteins c-sis
• Pyrrolidinones (pharmacology)
• Rats
• Rats, Inbred WKY
• Thiobarbituric Acid Reactive Substances (metabolism)