| 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
|
| Resource |
| Rats |
|
