Redox-Sensing Release of Human Thioredoxin from T Lymphocytes with Negative Feedback Loops
Abstract
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.
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Secretion of thioredoxin is a response to increased oxidative stress which can be inhibited by antioxidants.
“It has been proposed that the secretion of TRX is a response to increased oxidative stress which can be inhibited by the antioxidants (Kondo et al. 2004).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Kondo et al. 2004
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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
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- Authors
- Kondo, N., Ishii, Y., Kwon, Y.-W., Tanito, M., Horita, H., Nishinaka, Y., Nakamura, H., & Yodoi, J.
- Affiliations
- Kyoto University (JP)
- National Institute of Advanced Industrial Science and Technology (JP)
- Kyoto University Hospital (JP)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-01-01
- Volume
- 172
- Issue
- 1
- Pages
- 442-448
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1523887533
- Cited by
- 116
- References
- 35
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 7 · 2014: 6 · 2013: 6 · 2012: 7
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Keywords
- thioredoxin, T cells, protein secretion, redox sensing, hydrogen peroxide, oxidative stress, negative feedback loop, reactive oxygen species, caspase-3, N-acetylcysteine, Jurkat cells
- MeSH terms
- Binding Sites, Cell Line, Transformed, Humans, Hydrogen Peroxide, Oxidation-Reduction, Recombinant Proteins, T-Lymphocytes, Thioredoxins, Transfection, Human T-lymphotropic virus 1, Signal Transduction, Apoptosis, Oxidative Stress, Jurkat Cells, Feedback, Physiological, Extracellular Fluid
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