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阻断泛素-蛋白酶体通路对不同类型细胞具有完全不同的结果,但未见对原代白血病细胞作用的报道.观察了阻断上述通路对8例白血病患者和10例正常人骨髓单个核细胞（MNC）的作用.结果表明,不同个体原代白血病细胞对阻断此通路的反应敏感性存在明显差异,其中3例细胞极为敏感,24h以内90％细胞被迅速诱发凋亡,而正常人骨髓MNC对阻断泛素蛋白酶体通路反应不敏感,未观察到凋亡现象发生.进一步的免疫印迹实验发现,对上述通路敏感的原代白血病细胞Bcl-2蛋白表达量较高,而且在凋亡过程中发生了特异位点的酶解;对上述通路不敏感的细胞（包括正常人骨髓MNC）Bcl-2蛋白低表达,或Bcl-2高表达但未能检测到其特异性酶解现象.结合其他实验结果,提示细胞中Bcl-2蛋白是否发生特异位点酶解与细胞对阻断上述通路的敏感性之间具有相关性,为进一步研究不同种类细胞对阻断泛素-蛋白酶体通路敏感性差异的机制提供了线索.
Blocking the ubiquitin - proteasome pathway has completely different results for different types of cells, but no effect on primary leukemia cells was reported.Observation of the pathway blocking 8 leukemia patients and 10 cases of normal human bone marrow mononuclear cells (MNC) .Results showed that the sensitivity of different primary human leukemia cells to blocking this pathway was significantly different, of which 3 cells were extremely sensitive, 90% cells were rapidly induced apoptosis within 24h, while the normal human bone marrow MNC was not sensitive to blocking the ubiquitin proteasome pathway, and no apoptosis was observed.Further Western blotting showed that the expression of Bcl-2 protein in primary leukemic cells sensitive to these pathways was higher than that in apoptosis The site-specific enzymatic digestion of Bcl-2 protein or Bcl-2 was not detected in the cells that were not sensitive to the above pathways (including normal human bone marrow MNC). Combined with other experimental results, suggesting that there is a correlation between the specific site of Bcl-2 protein digestion and cell sensitivity to block the above pathway, in order to further study the different types of cell pairs Clues to the mechanism by which ubiquitin-proteasome pathway differences are blocked are provided.