Insulin and insulin-like growth factor I induce c-fos expression in postmitotic neurons by a protein kinase C-dependent pathway.
Insulin and insulin-like growth factor I induce c-fos expression in postmitotic neurons by a protein kinase C-dependent pathway.
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胰岛素和胰岛素样生长因子 I 通过蛋白激酶 C 依赖性途径诱导有丝分裂后神经元中的 c-fos 表达。
DOI：
10.1016/s0021-9258(18)82384-5
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
L. J. Robinson
中科院分区：
文献类型：
--
作者：
K. Heidenreich;T. Zeppelin;L. J. Robinson
最近的研究表明，胰岛素和胰岛素样生长因子调节神经系统的发育。介导对这些肽的神经营养反应的信号转导途径在很大程度上是未知的。本研究旨在观察胰岛素和胰岛素样生长因子I（IGF-I）对鸡胚前脑有丝分裂后神经元c-fos mRNA表达的调控，并探讨蛋白激酶C（PKC）在这些生长因子诱导c-fos表达中的作用。用生长因子或其他已知的c-fos基因表达激活剂处理培养的神经元，然后分离总细胞RNA并使用全长小鼠c-fos cDNA探针通过北方分析进行分析。胎牛血清、胰岛素、IGF-I、12-O-十四烷酰佛波醇（TPA）和放线菌酮诱导神经元中的2.2-脱氢酶c-fos转录。早在加入胰岛素后15分钟，c-fos mRNA水平就明显增加。水平在60分钟后达到峰值，然后保持高水平至180分钟。IGF-I诱导的c-fos的发病与胰岛素相似，但是，反应更短暂。剂量-反应曲线分析表明，胰岛素和IGF-I刺激c-fos的表达与自己的受体类型相互作用。胰岛素或IGF-I对c-fos mRNA的衰减率没有影响。在加入胰岛素之前用放线菌素D（2 μ M）预处理神经元5分钟完全阻断c-fos mRNA的诱导。TPA增加c-fos mRNA水平与胰岛素和IGF-I的动力学相似;然而，衰减阶段更接近胰岛素。两种PKC抑制剂鞘氨醇和星形孢菌素完全阻断了胰岛素、IGF-I和TPA对c-fos mRNA的诱导。这些数据表明胰岛素和IGF-I通过PKC介导的途径刺激神经元中c-fos基因的转录。AP-1活性增加可能介导对胰岛素和IGF-I的一些神经营养反应。
Recent studies indicate that insulin and insulin-like growth factors regulate development of the nervous system. The signal transduction pathways that mediate the neurotrophic responses to these peptides are largely unknown. The aims of this study were to examine the regulation of c-fos mRNA expression by insulin and insulin-like growth factor I (IGF-I) in postmitotic neurons derived from fetal chick forebrain and to investigate the role of protein kinase C (PKC) in c-fos induction by these growth factors. Cultured neurons were treated with growth factors or other known activators of c-fos gene expression, and then total cellular RNA was isolated and analyzed by Northern analysis using a full-length mouse c-fos cDNA probe. Fetal calf serum, insulin, IGF-I, 12-O-tetradecanoylphorbol (TPA), and cycloheximide induced a 2.2-kilobase c-fos transcript in neurons. Increased levels of c-fos mRNA were apparent as early as 15 min after the addition of insulin. Levels peaked after 60 min and then remained high up to 180 min. The onset of c-fos induction by IGF-I was similar to insulin; however, the response was more transient. Analyses of dose-response curves indicate that insulin and IGF-I stimulate c-fos expression by interacting with their own receptor type. The decay rate of c-fos mRNA was unaltered by insulin or IGF-I. Pretreatment of neurons with actinomycin D (2 microM) for 5 min prior to the addition of insulin completely blocked the induction of c-fos mRNA. TPA increased c-fos mRNA levels with similar kinetics to that of insulin and IGF-I; however, the attenuation phase more closely paralleled that of insulin. Two inhibitors of PKC, sphingosine and staurosporine, completely blocked the induction of c-fos mRNA by insulin, IGF-I, and TPA. These data indicate that insulin and IGF-I stimulate transcription of the c-fos gene in neurons by a PKC-mediated pathway. Increased AP-1 activity may mediate some of the neurotrophic responses to insulin and IGF-I.