Effects of a diabetogenic strain of encephalomyocarditis (EMC) virus on protein synthesis in mouse islets of Langerhans.

Effects of a diabetogenic strain of encephalomyocarditis (EMC) virus on protein synthesis in mouse islets of Langerhans.
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脑心肌炎 (EMC) 病毒致糖尿病株对小鼠朗格汉斯胰岛蛋白质合成的影响。

DOI:
10.1042/bj2700777
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发表时间:
1990
期刊:
The Biochemical journal
影响因子:
--
通讯作者:
K. Taylor
K. Taylor
中科院分区:
--
文献类型:
--
作者:
T. Ward;M. Clemens;K. Taylor

文献摘要

被引文献

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在组织培养中研究了脑心肌炎(EMC)病毒致糖尿病株对小鼠胰岛总蛋白和胰岛素生物合成的影响。在分散的小鼠胰岛中,通过测量[3 H]亮氨酸掺入蛋白质来评估蛋白质生物合成的速率。在20 mM葡萄糖中孵育的感染的分散胰岛中,胰岛素和总蛋白的生物合成在6 h时均降低;仅胰岛素生物合成在3 h时显著降低。在整个胰岛中,EMC病毒引起的葡萄糖刺激蛋白和胰岛素生物合成的减少,早在2小时后感染,而不伴随胰岛素释放的影响。这种蛋白质生物合成的抑制在感染后20 h仍然明显,此时发现胰岛素释放显著升高,胰岛胰岛素含量适度降低。在感染后44小时,葡萄糖诱导的胰岛素生物合成被优先抑制。在这个较晚的时间点,感染的胰岛也显示出胰岛素释放水平升高,以及胰岛胰岛素含量的显著损失。当使用适当的cDNA探针通过斑点杂交评估胰岛素mRNA和3-磷酸甘油醛脱氢酶(GAPDH)mRNA水平时,胰岛素mRNA水平在感染的前20小时内稳定下降,与GAPDH mRNA水平相反。在感染后44 h,两种类型的mRNA均显著降低。这表明,有一个最初的早期“关闭”的蛋白质合成没有其他可检测到的变化,胰岛功能。随后是胰岛素mRNA水平和胰岛素合成均显著降低的阶段。
The effects of a diabetogenic strain of encephalomyocarditis (EMC) virus on total protein and insulin biosynthesis in mouse islets of Langerhans have been studied in tissue culture. In dispersed mouse islets, the rates of protein biosynthesis were assessed by measuring the incorporation of [3H]leucine into proteins. In infected dispersed islets incubated in 20 mM-glucose, both insulin and total protein biosynthesis were decreased at 6 h; only insulin biosynthesis was significantly decreased at 3 h. In whole islets, EMC virus brought about a decrease in glucose-stimulated protein and insulin biosynthesis as early as 2 h after infection without concomitant effects on insulin release. This inhibition of protein biosynthesis was still apparent at 20 h post-infection, at which time insulin release was found to be markedly elevated, and the islet insulin content was moderately decreased. At 44 h post-infection, glucose-induced insulin biosynthesis was preferentially inhibited. Infected islets at this later time point also displayed elevated levels of insulin release, and a marked loss of islet insulin content. When insulin mRNA and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels were assessed by dot-blot hybridization using appropriate cDNA probes, levels of insulin mRNA were shown to decrease steadily during the first 20 h of infection, in contrast with the levels of GAPDH mRNA. At 44 h post-infection, both types of mRNA were markedly decreased. It is suggested that there is an initial early 'shut-off' of protein synthesis without other detectable changes in islet function. This is followed by a phase where both insulin mRNA levels and insulin synthesis are dramatically decreased.