The effect of proteasome inhibitors on mammalian erythroid terminal differentiation
The effect of proteasome inhibitors on mammalian erythroid terminal differentiation
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DOI：
10.1016/s0301-472x(02)00826-3
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发表时间：
2002-07-01
影响因子：
2.6
通讯作者：
Koury, ST
中科院分区：
文献类型：
--
作者：
Chen, CY;Pajak, L;Koury, ST
Objective.用Friend病毒的贫血诱导株（FVA细胞）感染的小鼠成红细胞在体外培养48小时后响应于促红细胞生成素（EPO）终末分化为网织红细胞阶段。本研究的目的是确定蛋白酶体介导的蛋白水解在FVA细胞终末分化过程中的可能作用。蛋白酶体抑制剂MG 132和lactacystin用于干扰蛋白酶体在终末分化过程中的正常功能。蛋白酶体抑制剂对终末分化的影响通过联苯胺染色后的细胞形态学评价和Western印迹分析来定量。在培养后期用lactacystin或MG 132处理EPO刺激的FVA细胞增加了细胞核和胞浆泛素化蛋白的积累，并减少了细胞核挤出至对照组的40%以下。我们的研究结果表明，蛋白酶体降解泛素化蛋白质起着重要的作用，哺乳动物成红细胞去核。(C)2002年国际实验血液学学会。出版社：Elsevier Science Inc.
Objective. Murine erythroblasts infected with the anemia-inducing strain of Friend virus (FVA cells) terminally differentiate to the reticulocyte stage after 48 hours of culture in vitro in response to erythropoietin (EPO). The objective of this study was to determine the possible role of proteasome-mediated proteolysis during the terminal differentiation of FVA cells.Materials and Methods. The proteasome inhibitors MG132 and lactacystin were used to perturb the normal function of proteasomes during terminal differentiation. Effects of proteasome inhibitors on terminal differentiation were quantitated by evaluation of cellular morphology after benzidine staining and by Western blot analyses.Results. Treatment of EPO-stimulated FVA cells with lactacystin or MG132 at later periods of culture increased accumulations of nuclear and cytosolic ubiquitinated proteins and decreased nuclear extrusion to less than 40% of controls.Conclusion. Our results suggest that the proteasomal degradation of ubiquitinated proteins plays an important role in the enucleation of mammalian erythroblasts. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.