Discovery of gliotoxin as a new small molecule targeting thioredoxin redox system

Hee Shim Choi; Joong Sup Shim; Ju A. Kim; Sang Won Kang; Ho Jeong Kwon

doi:10.1016/j.bbrc.2007.05.139

Discovery of gliotoxin as a new small molecule targeting thioredoxin redox system

Hee Shim Choi, Joong Sup Shim, Ju A. Kim, Sang Won Kang, Ho Jeong Kwon

Department of Life Science

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

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 H₂O₂. The compound reduces H₂O₂ to H₂O by replacing the function of peroxiredoxin in vitro and decreases intracellular level of H₂O₂ in HeLa cells. The anti-oxidant activity of gliotoxin was further validated H₂O₂-mediated cellular phenotype of angiogenesis. The proliferation of endothelial cells was inhibited by the compound at nanomolar range. In addition, H₂O₂-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.

Original language	English
Pages (from-to)	523-528
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	359
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2007.05.139
State	Published - 3 Aug 2007

Bibliographical note

Funding Information:
This study was partially supported by grants from the Chemical Genomics program from the Korean Ministry of Science and Technology and from the Brain Korea 21 Project, Republic of Korea.

Keywords

Anti-angiogenesis
Anti-oxidant
Gliotoxin
Thioredoxin redox system

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10.1016/j.bbrc.2007.05.139

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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 H2O2. The compound reduces H2O2 to H2O by replacing the function of peroxiredoxin in vitro and decreases intracellular level of H2O2 in HeLa cells. The anti-oxidant activity of gliotoxin was further validated H2O2-mediated cellular phenotype of angiogenesis. The proliferation of endothelial cells was inhibited by the compound at nanomolar range. In addition, H2O2-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.",

keywords = "Anti-angiogenesis, Anti-oxidant, Gliotoxin, Thioredoxin redox system",

author = "Choi, {Hee Shim} and Shim, {Joong Sup} and Kim, {Ju A.} and Kang, {Sang Won} and Kwon, {Ho Jeong}",

note = "Funding Information: This study was partially supported by grants from the Chemical Genomics program from the Korean Ministry of Science and Technology and from the Brain Korea 21 Project, Republic of Korea.",

year = "2007",

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doi = "10.1016/j.bbrc.2007.05.139",

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AU - Choi, Hee Shim

AU - Shim, Joong Sup

AU - Kim, Ju A.

AU - Kang, Sang Won

AU - Kwon, Ho Jeong

N1 - Funding Information: This study was partially supported by grants from the Chemical Genomics program from the Korean Ministry of Science and Technology and from the Brain Korea 21 Project, Republic of Korea.

PY - 2007/8/3

Y1 - 2007/8/3

N2 - 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 H2O2. The compound reduces H2O2 to H2O by replacing the function of peroxiredoxin in vitro and decreases intracellular level of H2O2 in HeLa cells. The anti-oxidant activity of gliotoxin was further validated H2O2-mediated cellular phenotype of angiogenesis. The proliferation of endothelial cells was inhibited by the compound at nanomolar range. In addition, H2O2-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.

AB - 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 H2O2. The compound reduces H2O2 to H2O by replacing the function of peroxiredoxin in vitro and decreases intracellular level of H2O2 in HeLa cells. The anti-oxidant activity of gliotoxin was further validated H2O2-mediated cellular phenotype of angiogenesis. The proliferation of endothelial cells was inhibited by the compound at nanomolar range. In addition, H2O2-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.

KW - Anti-angiogenesis

KW - Anti-oxidant

KW - Gliotoxin

KW - Thioredoxin redox system

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

Discovery of gliotoxin as a new small molecule targeting thioredoxin redox system

Abstract

Bibliographical note

Keywords

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