Cycloheximide induces stromelysin mRNA in cultured human fibroblasts.

Cycloheximide induces stromelysin mRNA in cultured human fibroblasts.
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Cycloheximide 在培养的人成纤维细胞中诱导溶基质素 mRNA。

DOI:
10.1111/j.1432-1033.1990.tb19197.x
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发表时间:
1990
期刊:
European journal of biochemistry
影响因子:
--
通讯作者:
HarrisJr,ED
HarrisJr,ED
中科院分区:
--
文献类型:
--
作者:
Otani,Y;Quinones,S;Saus,J;Kurkinen,M;HarrisJr,ED

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基质分解酶是一种金属蛋白酶,能降解细胞外基质大分子,包括纤维连接蛋白、层粘连蛋白、IV型胶原和蛋白多糖。我们现在报道,放线菌酮,一种蛋白质合成的抑制剂,以时间和剂量依赖的方式在成纤维细胞培养中诱导人基质分解素mRNA。Northern杂交结果显示,放线菌酮处理24小时后,基质分解素基因的表达水平较对照增加约20倍。在体外翻译或去除放线菌素后的细胞内翻译中,免疫沉淀的基质分解素水平增加,这表明放线菌素诱导的基质分解素基因是有功能的。对信使核糖核酸的稳定性分析表明,放线菌酮的作用部分是由于基质分解素基因的激活。与这些结果相反,放线菌酮不能诱导胶原酶β的表达,但能阻止IL-1 DNA的诱导。这些数据为胶原酶和基质分解素基因的不协调调控提供了证据,并提示一个短暂的抑制蛋白可能在基质分解素基因的表达中发挥作用。
Stromelysin is a metalloproteinase that degrades extracellular matrix macromolecules including fibronectin, laminin, collagen IV and proteoglycans. We now report that cycloheximide, an inhibitor of protein synthesis, induces human stromelysin mRNA in fibroblast cultures in a time‐ and dose‐dependent fashion. As determined by Northern hybridization, a 24‐h treatment with cycloheximide increased stromelysin mRNA about 20‐fold over the control level.In vitrotranslation or translation in cells after removal of cycloheximide resulted in increased levels of immunoprecipitable stromelysin suggesting that the cycloheximide‐induced stromelysin mRNA was functional. Analysis of mRNA stability suggested that the cycloheximide effect is in part due to the increased activation of the stromelysin gene. In contrast to these results, cycloheximide did not induce collagenase mRNA but, rather, prevented its induction by interleukin‐1β. These data provide evidence for discoordinate regulation of collagenase and stromelysin genes and suggest that a short‐lived repressor protein may play a role in the stromelysin gene expression.
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