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Effect of dibutyryl cyclic AMP and isoproterenol on 7β‐hydroxycholesterol cytotoxicity and esterification in spontaneous transformed cell lines derived from astrocyte primary cultures
Author(s) -
Behr Patrick,
Kupferberg Alexandre,
Leray Claude,
Schellenbaum Laurence,
Urban Paul-Francis,
Vincendon Guy,
Mersel Marcel
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)81433-m
Subject(s) - metabolite , intracellular , cytotoxicity , chemistry , hydrolysis , biochemistry , cell culture , incubation , cholesteryl ester , primary metabolite , cholesterol , biology , in vitro , lipoprotein , genetics
Incubation of spontaneous transformed cells derived from astrocyte primary cultures with 30 μM 7β‐hydroxycholesterol (7β‐OH‐CH) which is lethal to the cells or with 150 μM isoproterenol reduces the intracellular level of cAMP (4‐ and 2‐fold respectively). Treatment of the cultures with 0.5 mM dibutyryl (db)‐cAMP and 7β‐OH‐CH increases 3‐fold the intracellular level of cAMP and both, db‐cAMP and isoproterenol, raise the lethal effect of 7β‐OH‐CH and its esterification on C‐3‐OH by naturally occurring fatty acids (metabolite). Kinetics 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 7β‐OH‐CH esterification, (iii) the cytotoxicity of 7β‐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.