26S proteasome inhibitors inhibit dexamethasone-dependent increase of tyrosine aminotransferase and tryptophan 2,3-dioxygenase mRNA levels in primary cultured rat hepatocytes
| Autor: | Chieko Saito, Masashi Hyuga, Youko Nagaoka, Shingo Niimi, Minako Furukawa, Nana Kawasaki, Taiichiro Seki, Mizuho Harashima, Toyohiko Ariga |
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| Rok vydání: | 2012 |
| Předmět: |
Lactacystin
Transfection Biology Molecular biology chemistry.chemical_compound Glucocorticoid receptor Tyrosine aminotransferase Epoxomicin chemistry Mechanism of action Proteasome polycyclic compounds medicine Electrophoretic mobility shift assay medicine.symptom hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Biophysical Chemistry. :348-356 |
| ISSN: | 2153-0378 2153-036X |
| DOI: | 10.4236/jbpc.2012.34043 |
| Popis: | Dexamethasone (Dex), a ligand for transcriptional enhancement of tyrosine aminotransferase (TAT) and tryptophan 2,3-dioxygenase (TO) genes, (100 nM) maximally increased these mRNA levels at 12 h and 7 h in primary cultured rat hepatocytes and the nuclear fraction, respectively. Lactacystin (5 μM) and epoxomicin (0.5 μM), 26S proteasome inhibitors, significantly suppressed the Dex-dependent maximum increase of TAT and TO mRNA levels in the cells and the nuclear fraction. Electrophoretic mobility shift assay demonstrated that lactacystin did not affect binding of glucocorticoid receptor to glucocorticoid responsive element. Furthermore, lactacystin did not affect the activation of GRE luciferase reporter by Dex transfected to the cells. The results demonstrate that 26S proteasome is positively involved in the Dex-dependent increase of TAT and TO mRNA levels in the cells and suggest that the mechanism of action of 26S proteasome may be degradation of some RNase(s), which breaks down TAT and TO mRNAs. |
| Databáze: | OpenAIRE |
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