Redox-Sensing Release of Human Thioredoxin from T Lymphocytes with Negative Feedback Loops
| Autor: | Junji Yodoi, Masaki Tanito, Yong-Won Kwon, Yasuyuki Ishii, Norihiko Kondo, Hajime Nakamura, Yumiko Nishinaka, Hiroyuki Horita |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Signal peptide
animal structures T-Lymphocytes Immunology Apoptosis Biology Transfection Jurkat cells Jurkat Cells Thioredoxins Western blot Extracellular medicine Humans Immunology and Allergy Cell Line Transformed Feedback Physiological Human T-lymphotropic virus 1 Binding Sites medicine.diagnostic_test Extracellular Fluid Hydrogen Peroxide Recombinant Proteins Cell biology Oxidative Stress Cell culture Thioredoxin Signal transduction Oxidation-Reduction Signal Transduction |
| Zdroj: | The Journal of Immunology. 172:442-448 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Thioredoxin (TRX) is released from various types of mammalian cells despite no typical secretory signal sequence. We show here that a redox-active site in TRX is essential for its release from T lymphocytes in response to H2O2 and extracellular TRX regulates its own H2O2-induced release. Human T cell leukemia virus type I-transformed T lymphocytes constitutively release a large amount of TRX. The level of TRX release is augmented upon the addition of H2O2, but suppressed upon the addition of N-acetylcysteine. In the culture supernatant of a Jurkat transfectant expressing the tagged TRX-wild type (WT), the tagged TRX protein is rapidly released at 1 h and kept at a constant level until 6 h after the addition of H2O2. In contrast, another type of transfectant expressing the tagged TRX mutant (C32S/C35S; CS) fails to release the protein. H2O2-induced release of TRX from the transfectant is inhibited by the presence of rTRX-WT in a dose-dependent manner. Preincubation of the transfectant with rTRX-WT for 1 h at 37°C, but not 0°C, results in a significant suppression of the TRX release, reactive oxygen species, and caspase-3 activity induced by H2O2, respectively. Confocal microscopy and Western blot analysis show that extracellular rTRX-WT added to the culture does not obviously enter T lymphocytes until 24 h. These results collectively suggest that the oxidative stress-induced TRX release from T lymphocytes depends on a redox-sensitive event and may be regulated by negative feedback loops using reactive oxygen species-mediated signal transductions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|