title: Effects of U0126 on growth and activation of mitogen-activated protein kinases in Aspergillus fumigatus.
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.
  
  
  CONCLUSIONS
  U0126 shows promise as an antifungal candidate and the MAPK pathway may be a possible antifungal drug target for A. fumigatus.
authors: Department of Dermatology, Peking University First Hospital, Research Center for Medical Mycology, Peking University, Beijing 100034, China.
authors: Dong-Mei
authors: DM
authors: Ma
authors: Ya-Juan
authors: YJ
authors: Ji
authors: Fang
authors: F
authors: Yang
authors: Wei
authors: W
authors: Liu
authors: Zhe
authors: Z
authors: Wan
authors: Ruo-Yu
authors: RY
authors: Li
mesh_terms: D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D002070:Butadienes / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology*
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D020928:Mitogen-Activated Protein Kinases