期刊
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
卷 86, 期 9, 页码 606-612出版社
CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS
DOI: 10.1139/Y08-063
关键词
idiopathic pulmonary fibrosis; lysosomotropic drugs; glioblastoma; furin; epithelial cells; convertases
资金
- Canadian Institutes of Health Research
Transforming growth factor-beta (TGF beta) is synthesized as a precursor protein, pro-TGF beta, that Must be cleaved by a furin-like proteinase before it becomes biologically active. We hypothesized that alkalinization of the trans-Giolgi network (TGN)/endosome system may suppress pro-TGF beta processing and decrease TGFO secretion. This hypothesis was tested in human A549 alveolar epithelial and T98G glioblastoma cell lines and in C57BL/6 mice. Inhibition of furin-like activity with decanoyl-RVKR chloromethylketone suppressed pro-TGF beta processing, thereby significantly reducing the levels of secreted TGF beta. Brefeldin A, bafilomycin Al, ammonium chloride, and monensin also prevented pro-TGF beta processing. The alkalinizing lysosomotropic drugs chloroquine, hydroxychloroquine, amodlaquine. and azithromycin had a similar effect on the overall production of mature bioactive TGF beta. Reduced levels of secreted TGF beta were also associated with a decrease in Smad2 signaling. Mice treated with chloroquine showed a decrease in bronchoalveolar lavage fluid TGF beta. We conclude that alkalinizing lysosomotropic drugs inhibit pro-TGF beta processing.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据