Theophylline reduces the activity of cerebroside-sulfotransferase, a key enzyme in myelination, in cell cultures from newborn mouse brain.
Theophylline, a drug used in neonatology for the treatment of apnea, affects cholesterol synthesis if administered in concentrations of 10(-4) M (a concentration found in serum of treated patients) for 24 hr to dissociated brain cell cultures. The rate-limiting enzyme of cholesterol synthesis, beta-hydroxy-beta-methylglutaryl-coenzyme A reductase (EC 1.1.1.34), is lowered to 45% 48 hr after removal of theophylline. At the same time, cholesterol content of the cells is lowered to 73%. Inasmuch as the phospholipid content of the cells remains stable, the treatment changes the cholesterol phospholipid ratio. Concomitant to this effect, the activity of cerebroside-sulfotransferase (EC 2.8.2.11) is lowered to 60% of control values. We postulate that these two effects are linked to each other by means of modulation of the cerebroside-sulfotransferase activity by membrane lipids.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D002478:Cells, Cultured; D002554:Cerebrosides / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D051379:Mice; D009186:Myelin Sheath / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D015238:Sulfotransferases; D013466:Sulfurtransferases / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology*
D002554:Cerebrosides; D009419:Nerve Tissue Proteins; D010743:Phospholipids; D002784:Cholesterol; D013806:Theophylline; D006903:Hydroxymethylglutaryl CoA Reductases; D013466:Sulfurtransferases; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase