Protective roles of thioredoxin, a redox-regulating protein, in renal ischemia/reperfusion injury

Kasuno, Kenji; Nakamura, Hajime; Ono, Takahiko; Muso, Eri; Yodoi, Junji

doi:10.1046/j.1523-1755.2003.00224.x

Cited by 74 publications

(43 citation statements)

References 25 publications

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“…TRX is a 12 kDa protein with a highly conserved redox-active dithiol/disulfide active site sequence, Cys 32 -Gly-Pro-Cys 35 , which, together with GSH constitutes the major redox-regulating molecules that maintain cellular redox balance [16,17]. Several studies have demonstrated protective effect of TRX in diseases associated with increased oxidative stress such as post-ischaemic reperfusion injury, adriamycin-induced cardiotoxicity and diabetic nephropathy [18][19][20][21]. Additionally, while elevated serum levels of TRX are seen in patients with acute asthma exacerbations [22], the administration of exogenous TRX suppress AHR and airway inflammation in a murine model of asthma [23].…”

Section: Introductionmentioning

confidence: 99%

Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation

Torii

Wang

et al. 2010

Eur J Immunol

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Oxidative stress plays an important role in the pathogenesis of asthma via the upregulation of local inflammatory mediators and/or promoting Th2-skewing during Ag sensitization. Thioredoxin (TRX), a 12 kDa redox-active protein with antioxidative property, has been recently shown to play a protective role in various inflammatory diseases. Using a mouse model of asthma, we show here that IL-13 and eotaxin production are decreased in TRX-Tg mice leading to reduced eosinophils recruitment and mucus metaplasia. The reduction in airway inflammation occurs without the attenuation of systemic Th2 immunity in that comparable levels of Th2-type cytokines and Ig were detected in LN and serum, respectively, from TRX-Tg and WT mice. Likewise, CD4 1 T cells from both strains of mice developed similar Th1 and Th2 responses in vitro. Asthmatic lungs of TRX-Tg and WT mice contained similar amounts of GATA-3 1 and Foxp3 1 T cells. Finally, production of MIF, an upstream modulator of airway inflammation, was significantly reduced in the lungs of TRX-Tg mice. Our data suggest that TRX suppresses airway inflammation by inhibiting MIF production thereby limiting the downstream recruitment of eosinophils to the lung independently of modulating systemic Th1/Th2 immunity.

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Section: Introductionmentioning

confidence: 99%

Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation

Torii

Wang

et al. 2010

Eur J Immunol

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“…Overexpression of human TRX-1 in transgenic mice induces resistance to harmful conditions, including ischemic brain damage, adriamycin-induced cardiotoxicity, ischemia-reperfusion renal injury, and cerulein-induced pancreatitis (31)(32)(33)(34). More importantly, human TRX-1 transgenic mice are more resistant than control mice to proinflammatory cytokine-, bleomycin-, diesel exhaust particle-, or cigarette smoke-induced lung injury (19,35,36) and to influenza virus-induced pneumonia (18).…”

Section: Discussionmentioning

confidence: 99%

Redox-Active Protein Thioredoxin-1 Administration Ameliorates Influenza A Virus (H1N1)-Induced Acute Lung Injury in Mice

Yashiro

Tsukahara

Matsukawa

et al. 2013

Critical Care Medicine

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Objectives: Influenza virus infections can cause severe acute lung injury leading to significant morbidity and mortality. Thioredoxin-1 is a redox-active defensive protein induced in response to stress conditions. Animal experiments have revealed that thioredoxin-1 has protective effects against various severe disorders. This study was undertaken to evaluate the protective effects of recombinant human thioredoxin-1 (rhTRX-1) administration on influenza A virus (H1N1)-induced acute lung injury in mice.Design: Prospective animal trial. Setting: Research laboratory.Subjects: Nine-week-old male C57BL/6 mice inoculated with H1N1. Intervention:The mice were divided into vehicle-treated group and rhTRX-1-treated group. For survival rate analysis, the vehicle or rhTRX-1 was administered intraperitoneally every second day from Day -1 to Day 13. For lung lavage and pathological analyses, vehicle or rhTRX-1 was administered intraperitoneally on Day -1, 1, and 3. Measurements and Main Results:Lung lavage and pathological analyses were performed at 24, 72, and 120 hr after inoculation. The rhTRX-1 treatment significantly improved the survival rate of H1N1-inoculated mice, although the treatment did not affect virus propagation in the lung. The treatment significantly attenuated the histological changes and neutrophil infiltration in the lung of H1N1-inoculated mice. The treatment significantly attenuated the production of TNF-α and CXCL1 in the lung and oxidative stress enhancement which were observed in H1N1-inoculated mice. H1N1 induced expressions of TNF-α and CXCL1 in murine lung epithelial cells MLE-12, which were inhibited by the addition of rhTRX-1. The rhTRX-1 treatment started 30 min after H1N1 inoculation also significantly improved the survival of the mice. Conclusions:Exogenous administration of rhTRX-1 significantly improved the survival rate and attenuated lung histological changes in the murine model of influenza pneumonia. The protective mechanism of TRX-1 might be explained by its potent antioxidative and anti-inflammatory actions. Consequently, rhTRX-1 might be a possible pharmacological strategy for severe influenza virus infection in humans. 3Influenza virus infections cause a broad array of illnesses that are responsible for significant morbidity and mortality both in children and adults on a yearly basis (1). Influenza can cause periodic global pandemics with even higher penetrance of illness. Highly pathogenic avian influenza virus H5N1 emerged in 1996 in Hong Kong, China (2). Although cases of avian influenza infections have decreased since 2006, the emergence of a pandemic strain remains a threat. In 2009, novel swine-origin influenza virus H1N1 was identified in Mexico. It continues to spread globally (3).Several antiviral compounds have been developed against influenza virus to interfere with specific events in the replication cycle. Under treatment with these drugs, however, influenza virus infection occasionally causes severe pneumonia, necessitating intensive care and mechanical ventilat...

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“…26 Thioredoxin is secreted from proximal tubules into urine during renal ischemia-reperfusion and may have a protective effect against renal ischemiareperfusion injury. 27 Elevated thioredoxin reductase activity has been observed after exposure to lead acetate in rat kidneys along with other antioxidant enzymes such as catalase and superoxide dismutase. 28 In proximal tubules, nuclear and luminal localization was detected for thioredoxin 1 after ischemia-reperfusion injury.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2015

Exp Clin Transplant

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Objectives: Kidney allograft biopsies are performed after kidney transplant to determine graft dysfunction. We aimed to define and measure the oxidative stress occurring in these biopsies and compared these biopsies with donor pretransplant biopsies. Materials and Methods: The biopsy procedure was done according to the unit protocol. A core of tissue was taken for research purposes only when it was safe enough to proceed for an extra core. Common indications for biopsy were acute or chronic graft dysfunction, delayed graft function, acute cellular rejection, and calcineurin toxicity. There were 17 pretransplant biopsies taken from deceased-donor kidneys. Biopsy specimens were snap frozen immediately in liquid nitrogen and stored at -70°C. Samples were processed for Western blot and tested for markers of oxidative stress. Results: There were 61 biopsies analyzed. Oxidative stress enzymes were evaluated by Western blot including catalase, manganese superoxide dismutase, copper zinc superoxide dismutase, thioredoxin reductase, and thioredoxin. Upregulation of most antioxidant enzymes was observed in pretransplant biopsies. Increased expression of manganese superoxide dismutase was observed in donor kidneys and kidneys with acute cellular rejection and calcineurin toxicity. Copper zinc superoxide dismutase and catalase were elevated in donor and acute cellular rejection biopsies. Thioredoxin was elevated in donor biopsies and thioredoxin reductases were elevated in donor biopsies and biopsies with acute cellular rejection and calcineurin toxicity. Conclusions:The kidney allograft biopsies showed that oxidative stress levels were elevated during allograft dysfunction in all biopsies regardless of diagnosis, but not significantly. The levels also were elevated in pretransplant biopsies. The study showed that oxidative stress is involved in various acute injuries occurring within the allograft.

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Protective roles of thioredoxin, a redox-regulating protein, in renal ischemia/reperfusion injury

Abstract: The present findings suggest that TRX is retained in mTAL and secreted from proximal tubuli into urine during renal ischemia/reperfusion. The mTAL-specific retention of TRX may have a protective effect against renal ischemia/reperfusion injury.

Cited by 74 publications

References 25 publications

Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation

Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation

Redox-Active Protein Thioredoxin-1 Administration Ameliorates Influenza A Virus (H1N1)-Induced Acute Lung Injury in Mice

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