RECOMBINANT HUMAN INSULIN-LIKE GROWTH FACTOR-I EXERTS A TROPHIC ACTION AND CONFERS GLUTAMATE SENSITIVITY ON GLUTAMATE-RESISTANT CEREBELLAR GRANULE CELLS
RECOMBINANT HUMAN INSULIN-LIKE GROWTH FACTOR-I EXERTS A TROPHIC ACTION AND CONFERS GLUTAMATE SENSITIVITY ON GLUTAMATE-RESISTANT CEREBELLAR GRANULE CELLS
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DOI：
10.1073/pnas.90.18.8752
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发表时间：
1993-09-15
影响因子：
11.1
通讯作者：
MERCANTI, D
中科院分区：
文献类型：
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作者：
CALISSANO, P;CIOTTI, MT;MERCANTI, D
小脑颗粒细胞生长在血清复合物的存在下分化，但对兴奋性氨基酸的致死作用有抵抗力。当这些细胞也在胰岛素样生长因子I（IGF-I）的存在下生长时，它们变得对谷氨酸的毒性、致死作用完全敏感。IGF-I的谷氨酸增敏作用依赖于浓度（2-4 ng/ml时的半数最大效应）和时间（体外2-4天时的半数最大效应），并通过功能活性、谷氨酸激活的Ca 2+通道和电压门控Na+和晚期K+通道的出现而增强。IGF-I诱导的谷氨酸敏感性在去除该生长调节素后迅速可逆（t1/2 = 30-60 min）。IGF-I的作用不被IGF-II、神经生长因子、碱性或酸性成纤维细胞生长因子、血小板衍生生长因子或肿瘤坏死因子α所模拟。我们推测，小脑颗粒细胞的组成型是谷氨酸抗性，并成为兴奋性氨基酸的表观遗传线索的作用下，其中IGF-I可能是那些在体内操作之一。
Cerebellar granule cells grown in the presence of a serum complex differentiate but are resistant to the lethal action of excitatory amino acids. When these cells are grown also in the presence of insulin-like growth factor I (IGF-I) they become fully susceptible to the toxic, lethal action of glutamate. The glutamate-sensitizing action of IGF-I is dependent on concentration (half-maximal effect at 2-4 ng/ml) and time (half-maximal effect at 2-4 days in vitro) and is paralleled by the appearance of functionally active, glutamate-activated, Ca2+ Channels and of voltage-gated Na+ and late K+ channels. IGF-I-induced glutamate sensitivity is rapidly reversible (t 1/2 = 30-60 min) after removal of this somatomedin. The action of IGF-I is not mimicked by IGF-II, nerve growth factor, basic or acidic fibroblast growth factor, platelet-derived growth factor, or tumor necrosis factor alpha. We postulate that the constitutive phenotype of cerebellar granule cells is glutamate-resistant and becomes responsive to excitatory amino acids under the action of epigenetic cues among which IGF-I may be one of those operative in vivo.