Reference - Detail
| RRC ID | 128 |
|---|---|
| Author | Dutta KK, Nishinaka Y, Masutani H, Akatsuka S, Aung TT, Shirase T, Lee WH, Yamada Y, Hiai H, Yodoi J, Toyokuni S. |
| Title | Two distinct mechanisms for loss of thioredoxin-binding protein-2 in oxidative stress-induced renal carcinogenesis. |
| Journal | Lab Invest |
| Abstract |
Thioredoxin is a major component of thiol-reducing system. Recently, we identified thioredoxin-binding protein-2 (TBP-2) as a negative regulator of thioredoxin. Here, we report the role of TBP-2 in oxidative renal tubular injury and the subsequent carcinogenesis by ferric nitrilotriacetate. TBP-2 was abundantly expressed in the rat kidney. Immunohistochemical analysis revealed that TBP-2 was present in association with nuclei and mitochondrial intermembrane space in the proximal tubular cells and coimmunoprecipitated with cytochrome c. After acute oxidative tubular damage, TBP-2 protein, but not messenger RNA, markedly decreased, demonstrating shortened half-life of this protein. Most cases of the induced renal cell carcinoma showed undetectable levels of TBP-2 protein, which was associated with the methylation of CpG island in the promoter region. Genome sequence analyses identified the poly-A tract in the 3' untranslated region as a mutation hot spot in this rather nonselective environment. Collectively, the amounts of TBP-2 protein were inversely associated with proliferation of tubular cells, as evaluated by proliferating cell nuclear antigen. These results suggest that loss of TBP-2 is essential for proliferation of not only neoplastic but also non-neoplastic renal tubular cells, and that TBP-2 is a target gene in oxidative stress-induced renal carcinogenesis by ferric nitrilotriacetate. |
| Volume | 85(6) |
| Pages | 798-807 |
| Published | 2005-6-1 |
| DOI | 10.1038/labinvest.3700280 |
| PII | 3700280 |
| PMID | 15834431 |
| MeSH | Animals Base Sequence Carcinoma, Renal Cell / chemically induced Carcinoma, Renal Cell / genetics* Carcinoma, Renal Cell / pathology Carrier Proteins / genetics* Cell Cycle Proteins Cell Division DNA Mutational Analysis DNA Primers Kidney Neoplasms / chemically induced Kidney Neoplasms / genetics* Kidney Neoplasms / pathology Male Molecular Sequence Data Nitrilotriacetic Acid* Oxidative Stress* RNA, Messenger / genetics Rats Rats, Wistar |
| IF | 4.197 |
| Times Cited | 71 |
| WOS Category | PATHOLOGY MEDICINE, RESEARCH & EXPERIMENTAL |
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| The most frequently cited source | Youtube |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
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