Cholesterol hydroperoxides inhibit calmodulin and suppress atherogenesis in rabbits.

Abstract

A mixture of cholesterol autoxidation products, prepared from an aged sample of cholesterol by recrystallization from methanol, inhibits calmodulin irreversibly in a Ca2+-dependent reaction. Inhibitory activity is lost after treatment with NaBH4, NaCNBH3, or NaI, from which we conclude that calmodulin inhibition is due to one or more cholesterol hydroperoxides. Partially purified cholesterol hydroperoxides, with or without cholesterol, were fed to young adult white rabbits. Cholesterol in the diet caused extensive atheroma formation in the aortas, but the addition of cholesterol hydroperoxides markedly reduced lesion formation. A cholesterol hydroperoxide preparation that was reduced by treatment with NaI was not effective in preventing atheroma formation. Cholesterol hydroperoxides did not lower cholesterol concentrations in blood plasma, liver, or heart.

• Authors: C L Tipton, P C Leung, J S Johnson, R J Brooks, D C Beitz
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 146 Issue 3 Pg. 1166-72 (Aug 14 1987) ISSN: 0006-291X [Print] United States
• PMID: 3619923 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calmodulin
• Cholesterol, Dietary
• Lipid Peroxides
• cholesterol hydroperoxide
• Cholesterol

Topics

• Aging
• Animals
• Aorta (drug effects, pathology)
• Arteriosclerosis (pathology, prevention & control)
• Calmodulin (antagonists & inhibitors)
• Cholesterol (analogs & derivatives, chemical synthesis, pharmacology)
• Cholesterol, Dietary (pharmacology)
• Diet, Atherogenic
• Lipid Peroxides (pharmacology)
• Rabbits