Theophylline Reduces the Activity of Cerebroside-Sulfotransferase, a Key Enzyme in Myelination, in Cell Cultures from Newborn Mouse Brain

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Abstract
Summary: 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, β-hydroxy-β-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. Speculation: Theophylline reduces cholesterol synthesis and content and by that cerebroside-sulfotransferase activity in dissociated brain cell cultures. This raises the question of whether theophylline could have similar effects in vivo.

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