Murry R, McLane J A, Gruener G
Graduate Neuroscience Program, Loyola University Stritch School of Medicine, Maywood, Illinois 60153.
Ann N Y Acad Sci. 1993 May 28;679:270-5. doi: 10.1111/j.1749-6632.1993.tb18307.x.
Treatment of Neuro2a cells with drugs known to affect the integrity of microfilaments and microtubules, as well as with a calcium ionophore produced damage to the cellular membrane that was quantifiable by measuring the release of LDH into the culture medium. Concurrent exposure of the cells to ORG 2766 was found to modulate the release of LDH in a dose- and time-dependent fashion. ORG 2766 treatment was also able to reduce the basal release of LDH into the culture medium. [table: see text] The ORG 2766-induced reduction in LDH release was not due to down-regulation of protein synthesis. The peptide produced significant increases in protein synthesis relative to control conditions at concentrations of 10(-11) to 10(-6) M with 10(-8) M being an optimal dose. SDS-PAGE and 2-D PAGE analysis showed that de novo synthesis of most polypeptides was increased by about 40%. Additionally, a family of polypeptides tentatively identified as actins appear to undergo ORG 2766-dependent post translational charge modifications. These data are consistent with the hypothesis that regulation of transcription and/or translation are mechanisms important to the neurotrophic actions of ORG 2766.
用已知会影响微丝和微管完整性的药物以及钙离子载体处理Neuro2a细胞，会对细胞膜造成损伤，这种损伤可通过测量乳酸脱氢酶（LDH）释放到培养基中的量来量化。发现细胞同时暴露于ORG 2766会以剂量和时间依赖性方式调节LDH的释放。ORG 2766处理还能够减少LDH释放到培养基中的基础水平。[表格：见正文]ORG 2766诱导的LDH释放减少并非由于蛋白质合成的下调。在浓度为10^(-11)至10^(-6) M时，该肽相对于对照条件下蛋白质合成显著增加，其中10^(-8) M为最佳剂量。十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳（SDS - PAGE）和二维聚丙烯酰胺凝胶电泳（2 - D PAGE）分析表明，大多数多肽的从头合成增加了约40%。此外，一类初步鉴定为肌动蛋白的多肽似乎经历了依赖于ORG 2766的翻译后电荷修饰。这些数据与以下假设一致，即转录和/或翻译的调节是对ORG 2766神经营养作用重要的机制。
