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- Arnér, Elias S J
(författare)
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Redox pioneer : Professor Arne Holmgren
- 2011
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Ingår i: Antioxidants and Redox Signaling. - Stockholm : Karolinska Institutet, Dept of Medical Biochemistry and Biophysics. - 1557-7716 .- 1523-0864.
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Tidskriftsartikel (refereegranskat)abstract
- Dr. Arne Holmgren (Ph.D., 1968) is recognized here as a redox pioneer, because he has published at least one article on redox biology that has been cited over 1000 times and has published at least 10 articles, each cited over 100 times. He is widely known for his seminal discoveries and in-depth studies of thioredoxins, thioredoxin reductases, and glutaredoxins. Dr. Holmgren, active throughout his career at Karolinska Institutet, Sweden, has led the field of research about these classes of proteins for more than 45 years, continuously building upon his sequence determination of Escherichia coli thioredoxin in the late 1960s and discovery of the thioredoxin fold in the 1970s. He discovered and named glutaredoxin and he determined the structure and function of several members of these glutathione-dependent disulfide oxidoreductases. He still continues to broaden the frontiers of knowledge of thioredoxin and glutaredoxin systems. The thioredoxin fold is today recognized as one of the most common protein folds and the intriguing complexity of redox systems, redox signaling, and redox control of cellular function is constantly increasing. The legacy of Dr. Holmgren's research is therefore highly relevant and important also in the context of present science. In a tribute to his work, questions need to be addressed toward the physiological importance of redox signaling and the impact of glutaredoxin and thioredoxin systems on health and disease. Dr. Holmgren helped lay the foundation for the redox biology field and opened new vistas in the process. He is truly a redox pioneer.
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| 2. |
- Locy, Morgan L, et al.
(författare)
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Thioredoxin reductase inhibition elicits Nrf2-mediated responses in Clara cells : implications for oxidant-induced lung injury
- 2012
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Ingår i: Antioxidants and Redox Signaling. - Stockholm : Karolinska Institutet, Dept of Medical Biochemistry and Biophysics. - 1557-7716 .- 1523-0864.
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Pulmonary oxygen toxicity contributes to lung injury in newborn and adult humans.We previously reported that thioredoxin reductase (TrxR1) inhibition with aurothioglucose (ATG) attenuates hyperoxic lung injury in adult mice. The present studies tested the hypothesis that TrxR1 inhibition protects against the effects of hyperoxia via nuclear factor E2-related factor 2 (Nrf2)-dependent mechanisms. Results: Both pharmacologic and siRNA-mediated TrxR1 inhibition induced robust Nrf2 responses in murine-transformed Clara cells (mtCC). While TrxR1 inhibition did not alter the susceptibility of cells to the effects of hyperoxia, glutathione (GSH) depletion after TrxR1 inhibition markedly enhanced the hyperoxic susceptibility of cultured mtCCs. Finally, in vivo data revealed dose-dependent increases in the expression of the Nrf2 target gene NADPH:quinone oxidoreductase 1 (NQO1) in the lungs of ATGtreated adult mice. Innovation: TrxR1 inhibition activates Nrf2-dependent antioxidant responses in mtCCs in vitro and in adult murine lungs in vivo, providing a plausible mechanism for the protective effects of TrxR1 inhibition in vivo. Conclusion: GSH-dependent enzyme systems in mtCCs may be of greater importance for protection against hyperoxic exposure than are TrxR-dependent systems. The induction of Nrf2 activation via TrxR1 inhibition represents a novel therapeutic strategy that attenuates oxidant-mediated lung injury. Similar expression levels of TrxR1 in newborn and adult mouse or human lungs broaden the potential clinical applicability of the present findings to both neonatal and adult oxidant lung injury.
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| 4. |
- Abdiu, Avni, 1963-, et al.
(författare)
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Thioredoxin blood level increases after severe burn injury
- 2000
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Ingår i: Antioxidants and Redox Signaling. - 1523-0864 .- 1557-7716. ; 2:4, s. 707-716
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the thioredoxin (TRX) levels in severely burned patients and the possible origin of TRX, based on the recent understanding that TRX is a potent antioxidant with cytoprotective functions. Serum and plasma samples from burns patients and healthy blood donors were collected during the first 10 post-bum days and analyzed in a sandwich TRX enzyme-linked immunosorbent assay (ELISA). The TRX levels found were correlated to a panel of blood tests. The presence of TRX in platelets was investigated by immunoelectron microscopy and Western blotting. TRX serum levels of the severely burned patients showed a significant increase, with a mean serum TRX concentration on the day of injury of 76.5 ▒ 19.5 ng/ml (mean ▒ SD) and on post-burn day one 122.6 ▒ 66.9 ng/ml, compared to control blood donor levels of 22.7 ▒ 12.2 ng/ml (p = 0.0041 and 0.0117, respectively). A second peak of increase was found on post-burn days 7 to 9 with a four- to five-fold rise in concentration compared to controls. TRX elevation correlated well with increased platelet (p = 0.007) and leukocyte counts (p = 0.002). We also demonstrated by immunoelectron microscopy and Western blotting the presence of TRX in platelets. In conclusion, our demonstration of TRX release in burn injuries indicates that the TRX system is involved in a rapid antioxidant defense, coagulation processes, cell growth, and control of the extracellular peroxide tone intimately linked to cytoprotection and wound healing in burns. One of the cell types that delivers TRX promptly and efficiently into the blood may be the platelet.
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| 5. |
- Aboye, Teshome Leta, et al.
(författare)
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Interlocking disulfides in circular proteins : toward efficient oxidative folding of cyclotides.
- 2011
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 14:1, s. 77-86
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Tidskriftsartikel (refereegranskat)abstract
- Cyclotides are ultrastable plant proteins characterized by the presence of a cyclic amide backbone and three disulfide bonds that form a cystine knot. Because of their extreme stability, there has been significant interest in developing these molecules as a drug design scaffold. For this potential to be realized, efficient methods for the synthesis and oxidative folding of cyclotides need to be developed, yet we currently have only a basic understanding of the folding mechanism and the factors influencing this process. In this study, we determine the major factors influencing oxidative folding of the different subfamilies of cyclotides. The folding of all the cyclotides examined was heavily influenced by the concentration of redox reagents, with the folding rate and final yield of the native isomer greatly enhanced by high concentrations of oxidized glutathione. Addition of hydrophobic solvents to the buffer also enhanced the folding rates and appeared to alter the folding pathway. Significant deamidation and isoaspartate formation were seen when oxidation conditions were conducive to slow folding. The identification of factors that influence the folding and degradation pathways of cyclotides will facilitate the development of folding screens and optimized conditions for producing cyclotides and grafted analogs as stable peptide-based therapeutics.
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| 8. |
- Allen, John
(författare)
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Superoxide as an obligatory, catalytic intermediate in photosynthetic reduction of oxygen by adrenaline and dopamine.
- 2003
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Ingår i: Antioxidants & Redox Signaling. - : Mary Ann Liebert Inc. - 1557-7716 .- 1523-0864. ; 5:1, s. 7-14
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Tidskriftsartikel (refereegranskat)abstract
- The superoxide anion radical is known to be the first product of photosynthetic reduction of oxygen mediated by a variety of electron carriers. The effectiveness of many of these electron carriers as herbicides, and the toxicity of the superoxide they produce, have been suggested to rule out oxygen reduction as a physiological component of normal photosynthesis. Here results with isolated spinach chloroplasts are presented that demonstrate that the related catecholamines adrenaline and dopamine mediate photosynthetic reduction of oxygen. Complete inhibition by added superoxide dismutase of light-dependent oxygen uptake by isolated chloroplasts and of the electron transport it supports indicates that superoxide is an obligatory catalytic intermediate, not a product, in adrenaline- and dopamine-mediated oxygen reduction. These compounds might function as chemical analogues of a proposed natural mediator, or oxygen-reducing factor, that allows oxygen reduction to participate in energy transduction in photosynthesis. The identity of the putative natural mediator and the role of oxygen reduction in photosynthesis are discussed. The fully oxidized form of adrenaline, adrenochrome, also acts as a mediator of photosynthetic oxygen uptake, but only by reducing oxygen to superoxide.
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