Decreased levels of myotonic dystrophy protein kinase (DMPK) and delayed differentiation in human myotonic dystrophy myoblasts
Decreased levels of myotonic dystrophy protein kinase (DMPK) and delayed differentiation in human myotonic dystrophy myoblasts
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DOI：
10.1016/s0960-8966(01)00226-7
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发表时间：
2001-11-01
影响因子：
2.8
通讯作者：
Puymirat, J
中科院分区：
文献类型：
--
作者：
Furling, D;Lemieux, D;Puymirat, J
建立了来自强直性肌营养不良（DM 1）胎儿的肌细胞培养物，以一方面确定DM 1成肌细胞的分化是否改变，另一方面确定DM 1肌细胞中强直性肌营养不良蛋白激酶（DMPK）蛋白的水平是否降低。从12周龄胎儿的四头肌分离的DM 1成肌细胞以与从未受影响的15周龄胎儿的四头肌分离的正常成肌细胞相似的速率增殖，但是它们的成熟被改变，如慢肌球蛋白重链蛋白水平降低所示。相反，波形蛋白、肌生成素和胚胎肌球蛋白重链的表达没有变化。在成肌细胞分化过程中，DMPK转录物的水平急剧增加，并且突变的DMPK转录物保留在肌细胞核中的离散灶中。与正常细胞相比，DM I细胞中85-kDa DMPK蛋白的水平降低约50%。我们的研究表明，DM 1成肌细胞成熟的延迟与突变DMPK转录本的核保留和DMPK蛋白水平的降低有关。(C)2001 Elsevier Science B. V.保留所有权利。
Muscle cell cultures derived from a myotonic dystrophy (DM1) fetus were established in order to determine on the one hand, whether the differentiation of DM1 myoblasts is altered and, on the other hand, whether the levels of myotonic dystrophy protein kinase (DMPK) protein is decreased in DM1 muscle cells. DM1 myoblasts isolated from a quadriceps of a 12-weeks old fetus proliferate at a similar rate as normal myoblasts isolated from a quadriceps of an unaffected 15-weeks old fetus but their maturation is altered as shown by the decreased levels in slow myosin heavy chain protein. In contrast, no change was observed in the expression of vimentin, myogenin and embryonic myosin heavy chain. The levels of DMPK transcripts sharply increased during myoblast differentiation and the mutant DMPK transcripts are retained in discrete foci in the nuclei of muscle cells. The levels of 85-kDa DMPK protein was reduced by about 50% in DM I cells compared with normal cells. Our study demonstrates that delay in DM1 myoblast maturation is associated with nuclear retention of mutant DMPK transcripts and decreased levels of DMPK protein. (C) 2001 Elsevier Science B.V. All rights reserved.