Trichinella spiralis infected skeletal muscle cells arrest in G2/M and cease muscle gene expression.

Trichinella spiralis infected skeletal muscle cells arrest in G2/M and cease muscle gene expression.
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DOI:
10.1083/jcb.121.4.785
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发表时间:
1993-05
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Jasmer DP
Jasmer DP
中科院分区:
其他
文献类型:
--
作者:
Jasmer DP

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旋毛虫感染会引起骨骼肌细胞的多种变化,包括细胞核肥大和肌肉特异性蛋白表达减少。对导致这些变化的潜在细胞过程进行了研究。在同步性肌肉感染中,从感染后2-5天开始,[~3H]胸腺嘧啶核苷被掺入感染细胞核中。标记的细胞核在感染后60天稳定地整合到感染细胞中,并且似乎起源于感染时存在的分化的骨骼肌核。这些细胞核的平均DNA含量约为4N,表明[~3H]胸腺嘧啶核苷的摄取反映了感染细胞在G2/M期的DNA合成和随后的长期悬浮。与这些变化相关的是,与正常肌肉相比,感染细胞中肌肉特异性基因转录本减少到<1-<0.1%。与正常肌肉相比,感染细胞中肌肉转录调控因子mygenin、MyoD1和ID的转录水平分别降低到~lt;10和~lt;1,而转录水平分别增加约250%,表明肌肉基因的转录失活。感染细胞中的DNA合成可能代表了导致该感染细胞表型表达的起始事件。
Infection by Trichinella spiralis causes a variety of changes in skeletal muscle cells including the hypertrophy of nuclei and decreased expression of muscle specific proteins. Potential cellular processes leading to these changes were investigated. In synchronized muscle infections, [3H]thymidine was incorporated into infected cell nuclei from 2-5 days post infection. Labeled nuclei were stably integrated into the infected cell up to 60 days post infection and appear to originate from differentiated skeletal muscle nuclei present at the time of infection. These nuclei were further shown to contain a mean DNA content of approximately 4N, indicating that the [3H]thymidine uptake reflects DNA synthesis and subsequent long-term suspension of the infected cell in the cell cycle at G2/M. Associated with these changes, muscle specific gene transcripts were reduced to < 1- < 0.1% in the infected cell compared to normal muscle. Transcript levels of the muscle transcriptional regulatory factors myogenin, MyoD1, and Id were reduced to < 10, < 1, and increased approximately 250%, respectively, in the infected cell compared to normal muscle, indicating transcriptional inactivation of muscle genes. DNA synthesis in the infected cell may represent the initiation event which leads to expression of this infected cell phenotype.