| RRC ID |
38922
|
| 著者 |
Makino Y, Okamoto K, Yoshikawa N, Aoshima M, Hirota K, Yodoi J, Umesono K, Makino I, Tanaka H.
|
| タイトル |
Thioredoxin: a redox-regulating cellular cofactor for glucocorticoid hormone action. Cross talk between endocrine control of stress response and cellular antioxidant defense system.
|
| ジャーナル |
J Clin Invest
|
| Abstract |
Adaptation to stress evokes a variety of biological responses, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and synthesis of a panel of stress-response proteins at cellular levels: for example, expression of thioredoxin (TRX) is significantly induced under oxidative conditions. Glucocorticoids, as a peripheral effector of the HPA axis, exert their actions via interaction with a ligand-inducible transcription factor glucocorticoid receptor (GR). However, how these stress responses coordinately regulate cellular metabolism is still unknown. In this study, we demonstrated that either antisense TRX expression or cellular treatment with H2O2 negatively modulates GR function and decreases glucocorticoid-inducible gene expression. Impaired cellular response to glucocorticoids is rescued by overexpression of TRX, most possibly through the functional replenishment of the GR. Moreover, not only the ligand binding domain but the DNA binding domain of the GR is also suggested to be a direct target of TRX. Together, we here present evidence showing that cellular glucocorticoid responsiveness is coordinately modulated by redox state and TRX level and propose that cross talk between neuroendocrine control of stress responses and cellular antioxidant systems may be essential for mammalian adaptation processes.
|
| 巻・号 |
98(11)
|
| ページ |
2469-77
|
| 公開日 |
1996-12-1
|
| DOI |
10.1172/JCI119065
|
| PMID |
8958209
|
| PMC |
PMC507704
|
| MeSH |
Animals
Antioxidants / metabolism*
Blotting, Northern
CHO Cells
COS Cells
Cricetinae
Cytokines / pharmacology
DNA-Binding Proteins / biosynthesis
DNA-Binding Proteins / physiology
Dexamethasone / pharmacology*
Diamide / pharmacology
Genes, Reporter
HeLa Cells
Humans
Hydrogen Peroxide / pharmacology*
Kinetics
Mammals
Neoplasm Proteins / pharmacology
Oxidation-Reduction
Oxidative Stress*
Polymerase Chain Reaction
Receptors, Glucocorticoid / biosynthesis
Receptors, Glucocorticoid / physiology*
Recombinant Proteins / biosynthesis
Recombinant Proteins / pharmacology
Thioredoxins / biosynthesis*
Transcription, Genetic / drug effects*
Transfection
|
| IF |
11.864
|
| 引用数 |
147
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539) |
