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Effect of dibutyryl cyclic AMP and isoproterenol on 7 beta-hydroxycholesterol cytotoxicity and esterification in spontaneous transformed cell lines derived from astrocyte primary cultures. | LitMetric

AI Article Synopsis

  • - Incubating astrocyte-derived transformed cells with 30 µM 7 beta-hydroxycholesterol (7 beta-OH-CH) is lethal, while 150 µM isoproterenol significantly decreases intracellular cAMP levels by 4- and 2-fold, respectively.
  • - Treatment with 0.5 mM dibutyryl-cAMP (db-cAMP) combined with 7 beta-OH-CH boosts cAMP levels threefold and enhances the cytotoxic effects of both compounds, with db-cAMP and isoproterenol impacting cholesteryl-3-esters hydrolysis differently.
  • - The findings suggest that high intracellular cAMP levels alter the hydrolysis of cholesteryl-

Article Abstract

Incubation of spontaneous transformed cells derived from astrocyte primary cultures with 30 microM 7 beta-hydroxycholesterol (7 beta-OH-CH) which is lethal to the cells or with 150 microM isoproterenol reduces the intracellular level of cAMP (4- and 2-fold respectively). Treatment of the cultures with 0.5 mM dibutyryl (db)-cAMP and 7 beta-OH-CH increases 3-fold the intracellular level of cAMP and both, db-cAMP and isoproterenol, raise the lethal effect of 7 beta-OH-CH and its esterification on C-3-OH by naturally occurring fatty acids (metabolite). Kinetic studies of net steryl-3-esters hydrolysis revealed that db-cAMP and isoproterenol lower that of cholesteryl-3-esters (2-fold) whereas the opposite is found for the metabolite. These data demonstrate that (i) high cAMP intracellular levels modulate differently the net hydrolysis of cholesteryl-3-esters and metabolite, (ii) isoproterenol acts otherwise than cAMP on 7 beta-OH-CH esterification, (iii) the cytotoxicity of 7 beta-OH-CH is linked to its own esterification. The accumulation of metabolite subsequent to db-cAMP or isoproterenol treatment as a result of acyl-CoA:cholesterol acyl transferase activation is discussed.

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Source
http://dx.doi.org/10.1016/0014-5793(92)81433-mDOI Listing

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