Abraham J H, Hansen G H, Seiler N, Schousboe A
PharmaBiotec Research Center, Dept. of Biochemistry A + C, Panum Institute, University of Copenhagen, Denmark.
Neurochem Res. 1993 Feb;18(2):153-8. doi: 10.1007/BF01474678.
Effects of polyamine depletion by alpha-difluoromethylornithine (DFMO) were studied on the GABA-agonist mediated enhancement of the morphological development of cultured rat cerebellar granule cells. An increase in the number of neurite extending cells and in the cytoplasmic density of organelles relevant for protein synthesis was observed upon culturing in the presence of 4,5,6,7-tetrahydro-isoxazole[5,4-c]pyridin-3-ol (THIP) for 4 days. The intracellular concentrations of putrescine, spermidine, and spermine in these cultures were similar to the concentrations of the polyamines observed in cultures grown in a plain culture medium for 1, 2, 3 or 4 days, respectively. Upon culturing in the simultaneous presence of THIP and DFMO, the concentrations of putrescine and spermadine were reduced to less than 20% of the levels in the controls. This depletion was associated with a severely impaired morphological development of the granule cell cultures. Thus, the number of neurite extending cells was reduced to 50% of the number in the control cultures upon culturing in the presence of DFMO alone or in combination with THIP. Moreover, the THIP mediated increase in the cytoplasmic density of rough endoplasmic reticulum, Golgi apparatus and different types of vesicles was prevented by the exposure to DFMO.
研究了α-二氟甲基鸟氨酸（DFMO）消耗多胺对γ-氨基丁酸（GABA）激动剂介导的培养大鼠小脑颗粒细胞形态发育增强的影响。在4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇（THIP）存在下培养4天后，观察到神经突延伸细胞数量增加以及与蛋白质合成相关的细胞器的细胞质密度增加。这些培养物中腐胺、亚精胺和精胺的细胞内浓度分别与在普通培养基中培养1、2、3或4天的培养物中观察到的多胺浓度相似。在同时存在THIP和DFMO的情况下培养时，腐胺和亚精胺的浓度降低至对照水平的20%以下。这种消耗与颗粒细胞培养物的形态发育严重受损有关。因此，在单独存在DFMO或与THIP联合存在的情况下培养时，神经突延伸细胞的数量减少至对照培养物中数量的50%。此外，暴露于DFMO可阻止THIP介导的粗面内质网、高尔基体和不同类型囊泡的细胞质密度增加。
