Vitamin D3 up-regulated protein 1 mediates oxidative stress via suppressing the thioredoxin function

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Title
Vitamin D3 up-regulated protein 1 mediates oxidative stress via suppressing the thioredoxin function
Author(s)
Eun Sung Junn; Seung Hyun Han; Joo Young Im; Young Yang; Eun Wie Cho; Hong Duck Um; Do Kyun Kim; Kang Woo Lee; Pyung Lim Han; Sue Goo Rhee; In Pyo Choi
Bibliographic Citation
Journal of Immunology, vol. 164, no. 12, pp. 6287-6295
Publication Year
2000
Abstract
As a result of identifying the regulatory proteins of thioredoxin (TRX), a murine homologue for human vitamin D3 up-regulated protein 1 (VDUP1) was identified from a yeast two-hybrid screen. Cotransfection into 293 cells and precipitation assays confirmed that mouse VDUP1 (mVDUP1) bound to TRX, but it failed to bind to a Cys32 and Cys35 mutant TRX, suggesting the redox- active site is critical for binding, mVDUP1 was ubiquitously expressed in various tissues and located in the cytoplasm. Biochemical analysis showed that mVDUP1 inhibited the insulin-reducing activity of TRX. When cells were treated with various stress stimuli such as H2O2 and heat shock, mVDUP1 was significantly induced. TRX is known to interact with other proteins such as proliferation-associated gene and apoptosis signal-regulating kinase 1. Coexpression of mVDUP1 interfered with the interaction between TRX and proliferation-associated gene or TRX and ASK-1, suggesting its roles in cell proliferation and oxidative stress. To investigate the roles of mVDUP1 in oxidative stress, mVDUP1 was overexpressed in NIH 3T3 cells. When cells were exposed to stress, cell proliferation was declined with elevated apoptotic cell death compared with control cells. In addition, c-Jun N-terminal kinase activation and IL-6 expression were elevated. Taken together, these results demonstrate that mVDUP1 functions as an oxidative stress mediator by inhibiting TRX activity.
ISSN
0022-1767
Publisher
Amer Assoc Immunologists
DOI
http://dx.doi.org/10.4049/jimmunol.164.12.6287
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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