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首页> 外文期刊>Journal of applied toxicology >Pro-apoptotic properties of morphine in neuroblastoma×glioma NG108-15 hybrid cells: Modulation by yohimbine
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Pro-apoptotic properties of morphine in neuroblastoma×glioma NG108-15 hybrid cells: Modulation by yohimbine

机译：吗啡在神经母细胞瘤×神经胶质瘤NG108-15杂交细胞中的促凋亡特性：育亨宾的调控

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摘要

Short-term incubation with pharmacologically relevant concentrations of morphine has been shown to transiently affect the metabolism and redox status of NG108-15 cells through δ-opioid receptor stimulation, but apparently did not provoke cell death. The present work tries to determine if incubation with morphine at longer time intervals (24h) provokes apoptosis and/or necrosis, as it has been described in other cell lines. We have also checked the potential modulatory role of yohimbine on these effects, on the basis of the previously described interactions between this drug and opioid receptor ligands. Incubation with morphine 0.1 and 10μM provoked the appearance of images compatible with apoptosis (bebbling, pyknotic cells with cytoplasmic and nuclear condensation) and necrosis (cells swollen with vacuolated cytoplasm lacking cell processes) that could be observed directly and/or after staining with methylene blue, crystal violet and propidium iodide/4',6-diamidino-2-phenylindole (IP/DAPI). Quantification of apoptosis by activation of caspases 3 and 7 and DNA fragmentation with the Tunel assay revealed a modest but significant increase after incubation with the two concentrations of morphine used. Co-incubation with 10μM yohimbine prevented all these effects of the opioid. The results extend previous findings of a yohimbine-sensitive, neurotoxic effect of morphine on NG108-15 cells.
机译：已显示与药理学相关浓度的吗啡短期孵育可通过δ阿片受体刺激短暂影响NG108-15细胞的代谢和氧化还原状态，但显然不会引起细胞死亡。如在其他细胞系中所描述的，本工作试图确定在较长时间间隔（24小时）内与吗啡一起孵育是否会引起细胞凋亡和/或坏死。我们还根据前述药物与阿片受体配体之间的相互作用，检查了育亨宾对这些作用的潜在调节作用。用吗啡0.1和10μM孵育会引起与细胞凋亡（起泡，具有细胞质和核浓缩的凝结细胞）和坏死（缺乏细胞过程的空泡细胞质溶胀的细胞）相容的图像外观，可以直接观察和/或用亚甲基蓝染色后观察到，结晶紫和碘化丙啶/ 4'，6-二mid基-2-苯基吲哚（IP / DAPI）。通过使用半胱氨酸蛋白酶3和7的激活以及通过Tunel分析进行的DNA片段化对凋亡的定量分析显示，在使用两种浓度的吗啡孵育后，适度但显着的增加。与10μM育亨宾共同孵育可预防阿片类药物的所有这些作用。该结果扩展了先前发现的吗啡对NG108-15细胞的育亨宾敏感性，神经毒性作用。

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