(−)‐Deprenyl Reduces PC12 Cell Apoptosis by Inducing New Protein Synthesis
(−)‐Deprenyl Reduces PC12 Cell Apoptosis by Inducing New Protein Synthesis
复制标题
(−)-Deprenyl 通过诱导新蛋白质合成减少 PC12 细胞凋亡
作者：
W. G. Tatton;W. Ju;D. Holland;C. Tai;M. Kwan
摘要：(−)-Deprenyl 是一种单胺氧化酶 (MAO)-B 抑制剂，已被证明可以增加神经元存活并改变星形胶质细胞或 PC12 细胞中的蛋白质合成和基因表达，而与 MAO-B 抑制无关。我们使用血清和神经生长因子撤除来诱导 PC12 细胞凋亡，以确定 (−)-丙炔苯丙胺是否通过减少细胞凋亡来增加神经元存活。 (−)-Deprenyl 以浓度依赖性方式减少细胞死亡和核小体间 DNA 降解，并且在浓度太低而无法抑制 MAO 时有效 (<10−9M)。 (+)-Deprenyl 不会增加 PC12 细胞的存活率，并且除帕吉林外，其他 MAO-A 和 MAO-B 抑制剂不会改变细胞凋亡。转录和翻译抑制表明，细胞凋亡的减少需要通过 (−)-丙肾上腺素诱导新的蛋白质合成。添加 (−)-丙炔苯丙胺后，如果转录维持 4 小时并翻译维持 6 小时，则可诱导存活率增加。研究结果表明，转录诱导可能是 (−)-deprenyl 的其他独立于 MAO 的作用的基础。
Abstract: (−)‐Deprenyl, a monoamine oxidase (MAO)‐B inhibitor, has been shown to increase neuronal survival and to alter protein synthesis and gene expression in astrocytic or PC12 cells independently of MAO‐B inhibition. We used serum and nerve growth factor withdrawal to induce apoptotic death in PC12 cells to determine whether (−)‐deprenyl increases neuronal survival by reducing apoptosis. (−)‐Deprenyl reduced both cell death and internucleosomal DNA degradation in a concentration‐dependent manner and was effective at concentrations too low to inhibit MAO (<10−9M). (+)‐Deprenyl did not increase PC12 cell survival, and, with the exception of pargyline, other MAO‐A and MAO‐B inhibitors did not alter apoptotic death. Transcriptional and translational inhibition showed that the reduction in apoptosis required the induction of new protein synthesis by (−)‐deprenyl. Increased survival was induced if transcription was maintained for 4 h and translation for 6 h after (−)‐deprenyl addition. The findings suggest that transcriptional induction may underlie the other MAO‐independent actions of (−)‐deprenyl.
丙炔苯丙胺对 DSP-4 诱导的神经毒性的保护与其对 MAO B 的抑制无关。
影响因子：
5
作者：
Finnegan,KT;Skratt,JJ;Irwin,I;DeLanney,LE;Langston,JW
通讯作者：
Langston,JW
鸡胚体内自然发生和诱导的神经元死亡需要蛋白质和 RNA 合成：细胞死亡基因作用的证据。
影响因子：
2.7
作者：
Oppenheim,RW;Prevette,D;Tytell,M;Homma,S
通讯作者：
Homma,S