Pierre M, Pomerance M, Gavaret J M, Mousset S, Toru-Delbauffe D, Pierre J
Unité de Recherche sur la glande Thyroïde et la Régulation Hormonale, INSERM U.96, Hopital de Bicêtre, Kremlin-Bicêtre, France.
Biochem Pharmacol. 1991 Jul 15;42(3):553-8. doi: 10.1016/0006-2952(91)90318-y.
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.
在星形胶质细胞的原代培养物中，甲基甲烷、2 - N - 甲基9 - 羟基玫瑰树碱乙酸盐、双特卡林、1 -（2 - 氯乙基）- 3 - 环己基 - 1 - 亚硝基脲和1,3 - 双（2 - 氯乙基）- 1 - 亚硝基脲（卡莫司汀）在不同程度上阻断了酸性成纤维细胞生长因子和胰岛素[或胰岛素样生长因子1（IGF1）]对S6激酶的激活作用。最具活性的药物卡莫司汀的作用具有时间和浓度依赖性。用50 microM卡莫司汀预处理细胞1小时可完全阻止生长因子对S6激酶的激活作用至少2天。未受刺激的细胞的S6激酶活性受到轻微影响。用卡莫司汀处理细胞也会强烈损害12 - O - 十四烷酰佛波醇13 - 乙酸酯对S6激酶的激活作用，而8 - 溴 - 环磷酸腺苷对其激活作用的影响则较小。环磷酸腺苷依赖性蛋白激酶以及磷脂和Ca(2+)依赖性蛋白激酶不受影响。卡莫司汀对IGF1与细胞表面受体的结合或细胞胞质溶胶的S6激酶活性没有直接影响。
