Cholesterol hydroperoxides inhibit calmodulin and suppress atherogenesis in rabbits |
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| Authors: | C L Tipton P C Leung J S Johnson R J Brooks D C Beitz |
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| Institution: | Department of Biochemistry and Biophysics, Iowa State University, Ames, Iowa 50011 USA;Department of Mechanical Engineering, Faculty of Engineering, Universitas Pancasila, Srengseng Sawah. Jagakarsa, 12640, DKI Jakarta, Indonesia;The Chinese University of Hong Kong, Prince of Wales Hospital, Department of Orthopaedics & Traumatology, Shatin, N.T, Hong Kong;Shanghai 9th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China;The Chinese University of Hong Kong, Prince of Wales Hospital, Department of Orthopaedics & Traumatology, Shatin, N.T, Hong Kong |
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| 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. |
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