Effect of dibutyryl cyclic AMP and isoproterenol on 7 beta-hydroxycholesterol cytotoxicity and esterification in spontaneous transformed cell lines derived from astrocyte primary cultures.
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.
Behr
P
P
Laboratoire de Neurobiologie Moléculaire des Interactions Cellulaires, Centre de Neurochimie du CNRS, Strasbourg, France.
Kupferberg
A
A
Leray
C
C
Schellenbaum
L
L
Urban
P F
PF
Vincendon
G
G
Mersel
M
M
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002788:Cholesterol Esters / Q000378:metabolism; D000242:Cyclic AMP / Q000032:analysis; D006888:Hydroxycholesterols / Q000378:metabolism / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D051381:Rats
D002788:Cholesterol Esters; D006888:Hydroxycholesterols; C011724:cholest-5-en-3 beta,7 alpha-diol; D003994:Bucladesine; D000242:Cyclic AMP; D007545:Isoproterenol