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首页> 外文期刊>Journal of cellular biochemistry. >Selective inhibition of endothelial cell proliferation by fumagillin is not due to differential expression of methionine aminopeptidases.
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Selective inhibition of endothelial cell proliferation by fumagillin is not due to differential expression of methionine aminopeptidases.

机译：烟曲霉素对内皮细胞增殖的选择性抑制不是由于蛋氨酸氨基肽酶的差异表达。

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摘要

The angiogenesis inhibitors fumagillin and TNP-470 selectively inhibit the proliferation of endothelial cells, as compared with most other cell types. The mechanism of this selective inhibition remains uncertain, although methionine aminopeptidase-2 (MetAP2) has recently been found to be a target for fumagillin or TNP-470, which inactivates MetAP2 enzyme activity through covalent modification. Primary cultures of human endothelial cells and six other non-endothelial cell types were treated with fumagillin to determine its effect on cell proliferation. Only the growth of endothelial cells was completely inhibited at low concentrations of fumagillin. MetAP1 and MetAP2 levels in these cells were investigated to determine whether differential enzyme expression plays a role in the selective action of fumagillin. Western blot analysis and RT-PCR data showed that MetAP1 and MetAP2 were both expressed in these different types of cells, thus, ruling out differential expression of MetAP1 and MetAP2 as an explanation for the cell specificity of fumagillin. Expression of MetAP2, but not of MetAP1, is regulated. Treatment of human microvascular endothelial cells (HMVEC) with fumagillin resulted in threefold increases of MetAP2 protein in the cells, while MetAP1 remained constant. Similar upregulation of MetAP2 by exposure to fumagillin was also observed in non-endothelial cells, eliminating this response as an explanation for cell specificity. Taken together, these results indicate that while MetAP2 plays a critical role in the effect of fumagillin on endothelial cell proliferation, differential endogenous expression or fumagillin-induced upregulation of methionine aminopeptidases is not responsible for this observed selective inhibition. Copyright 2000 Wiley-Liss, Inc.
机译：与大多数其他细胞类型相比，血管生成抑制剂富马洁林和TNP-470选择性抑制内皮细胞的增殖。尽管最近发现甲硫氨酸氨肽酶2（MetAP2）是烟曲霉素或TNP-470的靶标，但这种选择性抑制的机制仍不确定，后者通过共价修饰使MetAP2酶的活性失活。用烟曲霉素治疗人内皮细胞和其他六种非内皮细胞类型的原代培养物，以确定其对细胞增殖的影响。在低浓度的烟曲霉素中，仅内皮细胞的生长被完全抑制。研究了这些细胞中MetAP1和MetAP2的水平，以确定差异酶的表达是否在烟曲霉素的选择性作用中起作用。 Western印迹分析和RT-PCR数据表明MetAP1和MetAP2都在这些不同类型的细胞中表达，因此，排除了MetAP1和MetAP2的差异表达可以作为烟曲霉素的细胞特异性的解释。 MetAP2的表达，但不是MetAP1，受到调控。用烟曲霉素治疗人微血管内皮细胞（HMVEC）导致细胞中MetAP2蛋白增加三倍，而MetAP1保持恒定。在非内皮细胞中也观察到通过暴露于烟曲霉素而引起的MetAP2的类似上调，从而消除了这种反应，从而解释了细胞特异性。两者合计，这些结果表明，尽管MetAP2在烟曲霉素对内皮细胞增殖的影响中起关键作用，但差异的内源性表达或烟曲霉素诱导的蛋氨酸氨基肽酶上调与这种观察到的选择性抑制无关。版权所有2000 Wiley-Liss，Inc.

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