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Effects of U0126 on growth and activation of mitogen-activated protein kinases in Aspergillus fumigatus

MA Dong-mei JI Ya-juan YANG Fang LIU Wei WAN Zhe LI Ruo-yu

中华医学杂志(英文版)2013,Vol.126Issue(2):220-225,6.
中华医学杂志(英文版)2013,Vol.126Issue(2):220-225,6.DOI:10.3760/cma.j.issn.0366-6999.20121528

Effects of U0126 on growth and activation of mitogen-activated protein kinases in Aspergillus fumigatus

Effects of U0126 on growth and activation of mitogen-activated protein kinases in Aspergillus fumigatus

MA Dong-mei 1JI Ya-juan 1YANG Fang 1LIU Wei 1WAN Zhe 1LI Ruo-yu1

作者信息

  • 1. Department of Dermatology, Peking University First Hospital,Research Center for Medical Mycology, Peking University, Beijing 100034, China
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摘要

Abstract

Background Invasive aspergillosis (IA),which is mainly caused by Aspergillus fumigatus (A.fumigatus),is a major cause of morbidity and mortality in immunocompromised patients.Despite considerable progress in currently available antifungals the mortality still remains high in critically ill patients.U0126 which is a highly selective inhibitor of MEK1 and MEK2 in the RAF/MEK/ERK pathway in mammalian cells has been demonstrated to have an anti-proliferative role in cancer cells.The purpose of this study was to explore the role of U0126 on growth inhibition and activation of mitogen-activated protein kinases (MAPKs) in A.fumigatus.Methods Germination percentage and hyphae growth in A.fumigatus treated with U0126 were observed and compared with untreated controls.Western blotting analysis was used to detect changes in activation of SakA,MpkA and MpkB.Results U0126 inhibited germination and hyphae growth in A.fumigatus and enhanced the phosphorylation of SakA and MpkA under oxidative stress.U0126 at 10 μmol/L did not block the activation of MpkB during nitrogen starvation stress.Conclusion U0126 shows promise as an antifungal candidate and the MAPK pathway may be a possible antifungal drug target for A.fumigatus.

关键词

Aspergillus fumigatus/ protein kinase inhibitors/ mitogen-activated protein kinases

Key words

Aspergillus fumigatus/ protein kinase inhibitors/ mitogen-activated protein kinases

引用本文复制引用

MA Dong-mei,JI Ya-juan,YANG Fang,LIU Wei,WAN Zhe,LI Ruo-yu..Effects of U0126 on growth and activation of mitogen-activated protein kinases in Aspergillus fumigatus[J].中华医学杂志(英文版),2013,126(2):220-225,6.

基金项目

This project was sponsored by a grant from the National Foundation of Natural Sciences in China (No.30930006). (No.30930006)

中华医学杂志(英文版)

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0366-6999

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