McCormack S A, Viar M J, Johnson L R
Department of Physiology and Biophysics, University of Tennessee, College of Medicine, Memphis 38163.
Am J Physiol. 1993 Feb;264(2 Pt 1):G367-74. doi: 10.1152/ajpgi.1993.264.2.G367.
Studies from our laboratory have shown that polyamines are essential for the normal repair of duodenal erosions induced in vivo in a rat stress-ulcer model. In that model, the inhibition of ornithine decarboxylase, a rate-limiting enzyme of polyamine biosynthesis, with alpha-difluoromethylornithine (DFMO) almost entirely prevented healing. Healing could be restored by oral polyamines. In this paper, we have investigated whether the polyamines are required for the early stages of epithelial restitution using an IEC-6 cell culture model of cell migration. Treatment of the cells with DFMO for 4 days reduced cell migration 80%. Migration could be restored to normal by concomitant treatment with putrescine (PUT), spermidine (SPD), or spermine (SPM), but not by their addition during the migration period (6 h) only. If DFMO treatment was not begun until the migration period, it still reduced cell migration 20%, and this deficit could not be restored by concomitant addition of the polyamines. Intracellular polyamine levels at these times, i.e., 6 h or 4 days, were an important factor in these results. Only PUT was undetectable after 6 h of DFMO. SPD and SPM were still at normal levels at 6 h. SPD was undetectable at 4 days, but SPM was still at 40% of normal. These data give added importance to PUT because its absence reduced cell migration after only 6 h, while SPD and SPM were still present in normal amounts. Perhaps exogenous SPD and SPM restored cell migration when present with DFMO for 4 days treatment primarily because they contributed to intracellular PUT through the acetyltransferases.(ABSTRACT TRUNCATED AT 250 WORDS)
我们实验室的研究表明，多胺对于大鼠应激性溃疡模型体内诱导的十二指肠糜烂的正常修复至关重要。在该模型中，用α-二氟甲基鸟氨酸（DFMO）抑制鸟氨酸脱羧酶（多胺生物合成的限速酶）几乎完全阻止了愈合。口服多胺可恢复愈合。在本文中，我们使用IEC-6细胞迁移的细胞培养模型研究了上皮修复早期阶段是否需要多胺。用DFMO处理细胞4天可使细胞迁移减少80%。通过同时用腐胺（PUT）、亚精胺（SPD）或精胺（SPM）处理，迁移可恢复正常，但仅在迁移期（6小时）添加它们则不能恢复。如果直到迁移期才开始DFMO处理，它仍然会使细胞迁移减少20%，并且这种缺陷不能通过同时添加多胺来恢复。这些时间点（即6小时或4天）的细胞内多胺水平是这些结果的一个重要因素。DFMO处理6小时后仅PUT检测不到。SPD和SPM在6小时时仍处于正常水平。4天时SPD检测不到，但SPM仍为正常水平的40%。这些数据使PUT的重要性增加，因为仅6小时后其缺失就减少了细胞迁移，而此时SPD和SPM仍以正常量存在。也许外源性SPD和SPM在与DFMO一起处理4天时恢复细胞迁移，主要是因为它们通过乙酰转移酶促进了细胞内PUT的生成。（摘要截短于250字）
