Abstract
We have shown previously, that the activity of cerebrosulfotransferase (CST) a microsomal enzyme involved in myelin synthesis is modulated in vitro by the cholesterol-phospholipid ratio (C/P) in microsomal membranes. To further investigate this mechanism, we studied two different models: 1.) Removal of cholesterol by phospholipid micelles and 2.) Inhibition of cholesterol synthesis in cultivated brain cells. 1. We incubated mouse brain microsomes from 14 day old animals with phospholipid micelles, which caused a decrease of C/P from 0.60 to 0.53 (Aequivalent age of 18 days). Under these conditions CST activity rose from 4'900 dpm to 9'800 dpm, aequivalent the activity of 18 day animals. Concomitant electrospin-resonance measurements showed an increase in membrane fluidity. 2. In C6 mouse glioblastoma cells cholesterol synthesis was temporarely inhibited by adding estradiol to the medium. This caused a decrease in C/P from 0.32 ±0.02 to 0.22±0.03 from 19 to 24 hours after the addition of the inhibitor. During this time CST activity rose from 3200±340 dpm to 6'300±500 dpm. After this period C/P and CST activity returned to normal. We therefore speculate that microsomal CST activity is modulated by changes in membrane fluidity, which is caused by changes in the molar-ratio of cholesterol to phospholipid in microsomes.
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Herschkowitz, N., Siegrist, H., Jutzi, H. et al. Changes of microsomal membrane compositions modulate microsomal enzyme activity. Pediatr Res 13, 78 (1979). https://doi.org/10.1203/00006450-197901000-00052
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DOI: https://doi.org/10.1203/00006450-197901000-00052