MIMICRY AND INHIBITION OF NERVE GROWTH-FACTOR EFFECTS - INTERACTIONS OF STAUROSPORINE, FORSKOLIN, AND K252A IN PC12 CELLS AND NORMAL RAT CHROMAFFIN CELLS-INVITRO

被引：70

作者：

TISCHLER, AS ^{[1
]}

RUZICKA, LA ^{[1
]}

PERLMAN, RL ^{[1
]}

机构：

[1] UNIV CHICAGO,DEPT PEDIAT,CHICAGO,IL 60637

来源：

JOURNAL OF NEUROCHEMISTRY | 1990年 / 55卷 / 04期

关键词：

Chromaffin cells; K252a; Nerve growth factor; Neurites; PC12; cells; Staurosporine; Survival;

D O I：

10.1111/j.1471-4159.1990.tb03120.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Abstract: The structurally similar compounds staurosporine and K252a are potent inhibitors of protein kinases. K252a has previously been reported to inhibit most or all of the effects of nerve growth factor (NGF) on PC12 pheochromocytoma cells, and staurosporine has been reported both to inhibit and to mimic NGF‐induced neurite outgrowth from a PC12 cell subclone in a dose‐dependent manner. We have studied the interactions of these agents with each other, with NGF, and with forskolin, an activator of adenylate cyclase, on the parent PC12 cell line and on normal neonatal and adult rat chromaffin cells. Staurosporine alone or in conjunction with forskolin induces outgrowth of short neurites from PC12 cells but does not substitute for NGF in promoting cell survival. It does not abolish NGF‐induced neurite outgrowth but does reverse the effects of NGF on catecholamine synthesis. K252a abolishes NGF‐induced neurite outgrowth but only partially decreases outgrowth induced by NGF plus forskolin. It does not inhibit neurite outgrowth produced by staurosporine or staurosporine plus forskolin. These findings with PC12 cells suggest that staurosporine might act downstream from K252a and NGF on components of one or more signal transduction pathways by which NGF selectively affects the expression of certain traits. Both neonatal and adult rat chromaffin cells show dramatic flattening and extension of filopodia in response to staurosporine, an observation suggesting that some of the same pathways might remain active in cells that do not exhibit a typical NGF response. Only a small amount of neurite outgrowth is observed, however, and only in neonatal cultures. Staurosporine might be useful in studying both the actions of NGF and the ways in which those actions are altered in the course of normal development and tumor formation. Copyright © 1990, Wiley Blackwell. All rights reserved

引用

页码：1159 / 1165

页数：7

共 39 条

[1] LITHIUM ION INHIBITS NERVE GROWTH-FACTOR INDUCED NEURITE OUTGROWTH AND PHOSPHORYLATION OF NERVE GROWTH-FACTOR MODULATED MICROTUBULE-ASSOCIATED PROTEINS [J].