Serotonin uptake, storage, and synthesis in an immortalized committed cell line derived from mouse teratocarcinoma.

We report the isolation and characterization of a serotoninergic cell line, 1C11, derived from a mouse teratocarcinoma. The clone 1C11 was immortalized through the expression of the simian virus 40 oncogenes. 1C11 presents two states: an immature epithelial-like state (1C11 precursor) and a more differentiated state (1C11). After induction by dibutyryl cyclic AMP and cyclohexanecarboxylic acid, almost 100% of 1C11 cells continue to divide and have acquired a neural-like phenotype. 1C11* cells coexpress several neural markers, such as synaptophysin (the membrane constituent of synaptic vesicles), the neuropeptide [Met5]enkephalin, and the neurotransmitter serotonin. 1C11* cells store endogenous serotonin and are able to synthesize serotonin from L-tryptophan and to catabolize it by monoamine oxidase B. Moreover, the cells take up serotonin by a carrier-mediated mechanism very similar to that of serotoninergic neurons. The expression of the simian virus 40 oncogenes, which promoted immortalization, does not therefore prevent further differentiation. This inducible cell line constitutes a valuable model for cellular and molecular studies concerning the physiology and the pharmacological modulation of the serotoninergic phenotype. IMAGES:

本研究报道了一株源自小鼠畸胎瘤（mouse teratocarcinoma）的5-羟色胺能细胞系（serotoninergic cell line）1C11的分离与鉴定。该1C11克隆通过表达猿猴病毒40（simian virus 40）癌基因实现永生化。1C11细胞存在两种状态：未成熟类上皮状态（1C11前体细胞）与分化程度更高的成熟状态（1C11细胞）。经双丁酰环腺苷酸（dibutyryl cyclic AMP）与环己羧酸（cyclohexanecarboxylic acid）诱导后，近100%的1C11细胞仍可维持增殖，并获得了神经样表型。诱导后的1C11*细胞共表达多种神经标志物，包括突触囊泡膜蛋白（synaptophysin，即突触囊泡膜的组成成分）、[Met⁵]脑啡肽（[Met5]enkephalin）以及神经递质5-羟色胺。1C11*细胞可储存内源性5-羟色胺，能够以L-色氨酸（L-tryptophan）为底物合成5-羟色胺，并可通过单胺氧化酶B（monoamine oxidase B）对其进行代谢。此外，该细胞可通过载体介导的摄取机制摄取5-羟色胺，该机制与5-羟色胺能神经元的摄取过程极为相似。上述介导永生化的猿猴病毒40癌基因的表达，并未阻碍细胞的进一步分化。该可诱导细胞系可为围绕5-羟色胺能表型的生理学与药理学调控开展的细胞及分子研究提供极具价值的模型。图像：