Early effect of BCNU on rat astrocytes. Inhibition of S6 kinase activation by growth factors.
In primary cultures of astrocytes, methylmethane, 2-N-methyl 9-hydroxy-ellepticinium acetate, ditercalinium, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1,3 bis (2-chloroethyl)-1-nitrosourea (BCNU) blocked to various extents the activation of S6 kinase by acidic fibroblast growth factor and insulin [or insulin-like growth factor 1 (IGF1)]. The effects of the most active agent, BCNU, were time and concentration dependent. Pretreatment of cells with 50 microM BCNU for 1 hr completely prevented S6 kinase activation by growth factors for at least 2 days. The S6 kinase activity of unstimulated cells was slightly affected. S6 kinase activation by 12-O-tetradecanoylphorbol 13 acetate was also strongly impaired by treating cells with BCNU whereas activation by 8-bromo-cyclic AMP was slightly reduced. Cyclic AMP-dependent protein kinase and phospholipid and Ca(2+)-dependent protein kinase were unaffected. BCNU had no direct effect on IGF1 binding to cell surface receptors or on the S6 kinase activity of cell cytosols.
Pierre
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M
Unité de Recherche sur la glande Thyroïde et la Régulation Hormonale, INSERM U.96, Hopital de Bicêtre, Kremlin-Bicêtre, France.
Pomerance
M
M
Gavaret
J M
JM
Mousset
S
S
Toru-Delbauffe
D
D
Pierre
J
J
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology; D002227:Carbazoles / Q000494:pharmacology; D002330:Carmustine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D019893:Ribosomal Protein S6 Kinases; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002227:Carbazoles; D007328:Insulin; D047428:Protein Kinase Inhibitors; D016220:Fibroblast Growth Factor 1; D000242:Cyclic AMP; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases; D013755:Tetradecanoylphorbol Acetate; D002330:Carmustine; C042804:ditercalinium