title: Discovery of gliotoxin as a new small molecule targeting thioredoxin redox system.
abstract: Thioredoxin redox system has been implicated as an intracellular anti-oxidant defense system leading to reduction of cellular oxidative stresses utilizing electrons from NADPH. From high content screening of small molecules targeting the system, gliotoxin, a fungal metabolite, was identified as an active compound. Gliotoxin potently accelerates NADPH oxidation and reduces H(2)O(2). The compound reduces H(2)O(2) to H(2)O by replacing the function of peroxiredoxin in vitro and decreases intracellular level of H(2)O(2) in HeLa cells. The anti-oxidant activity of gliotoxin was further validated H(2)O(2)-mediated cellular phenotype of angiogenesis. The proliferation of endothelial cells was inhibited by the compound at nanomolar range. In addition, H(2)O(2)-induced tube formation and invasion of the cells were blocked by gliotoxin. Together, these results demonstrate that gliotoxin is a new small molecule targeting thioredoxin redox system.
authors.affiliation: Chemical Genomics Laboratory, Department of Biotechnology, College of Engineering, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors.forename: Hee Shim
authors.initials: HS
authors.lastname: Choi
authors.forename: Joong Sup
authors.initials: JS
authors.lastname: Shim
authors.forename: Ju-A
authors.initials: JA
authors.lastname: Kim
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Kang
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005912:Gliotoxin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism*; D014470:Umbilical Cord / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D013879:Thioredoxins; D005912:Gliotoxin; D006861:Hydrogen Peroxide; D009195:Peroxidase