Biomedical subjects

Junji Yodoi

Publications and source records attributed to Junji Yodoi.

119 records · Page 7Linked to original sources

PubMed2002

Successful immunoglobulin treatment for fulminant myocarditis and serial analysis of serum thioredoxin: a case report.

A 31-year-old woman suspected to have acute myocarditis was admitted to hospital and was managed with intra-aortic balloon pumping and a percutaneous cardiopulmonary support system because of sustained ventricular tachycardia. After immunoglobulin treatment, cardiac function and systematic inflammation were improved. The left ventricular endomyocardial biopsy revealed massive necrosis and degeneration of myocardial cells, and extensive infiltration of inflammatory cells. The clinicopathology of this patient was thought to be fulminant myocarditis. Serial serum thioredoxin (TRX) analysis showed that the serum level was high during the acute phase, and decreased during the chronic phase. Immunohistochemistry for TRX in the biopsy samples showed that inflammatory cells and cardiomyocytes were positively stained.

Acute Disease↗

PubMed2002

Redox Regulation by Thioredoxin and its Related Molecules.

Thioredoxin (Trx) is a small multifunctional protein with a redox active dithiol/disulfide in the active-site sequence Cys-Gly-Pro-Cys. Trx functions as a key molecule in the maintenance of cellular redox balance. In addition to the cytoprotective action against oxidative stresses, Trx is involved in various cellular processes including gene expression, signal transduction, proliferation and apoptosis. Recently, various proteins sharing Trx-like active-site sequences have been found and classified as part of the Trx superfamily. Trx and these Trx-related molecules constitute a cellular redox regulation system, and further studies to clarify their biological functions will provide new therapeutic strategies for the disorders caused or complicated by oxidative stresses. (c) 2002 Prous Science. All rights reserved.

Journal Article↗

PubMed2002

Cytoprotective effect of thioredoxin against retinal photic injury in mice.

PURPOSE: To determine the protective role of thioredoxin (TRX), an endogenous redox (reduction and oxidation) regulator, against retinal photic injury in mice. METHODS: Four-week-old BALB/c mice were exposed to white fluorescent light (8000 lux) for 2 hours. The number of both the photoreceptor cell nuclei and the TUNEL-positive photoreceptor cell nuclei were counted to determine the severity of damage. Expression of endogenous TRX was analyzed in the retinal samples by immunohistochemistry and Western blot. Recombinant (r)TRX or mutant rTRX, in which cysteines in the active site are replaced with serines, was injected intravitreously into BALB/c mice before light exposure. Oxidized and tyrosine-phosphorylated proteins were analyzed in retinal samples to examine the antioxidative effect of TRX. The number of photoreceptor cell nuclei and the DNA ladder in the retinal samples were analyzed. RESULTS: A significant reduction was observed in the number of photoreceptor cells and induction of TUNEL-positive nuclei after light exposure. TRX expression was enhanced in both the neural retina and retinal pigment epithelium after light exposure. The amounts of oxidized and tyrosine-phosphorylated proteins decreased in the neural retinas of the rTRX-treated mice compared with the vehicle- or mutant rTRX-treated mice. The reduction of photoreceptor cells and formation of a DNA ladder were suppressed by rTRX pretreatment but not with mutant rTRX. CONCLUSIONS: TRX is induced in the retinal tissue after light exposure. Intraocular injection of rTRX suppresses photo-oxidative stress. TRX intensification may be a useful therapeutic strategy to prevent retinal photic injury.

Animals↗

PubMed2002

Change of redox status and modulation by thiol replenishment in retinal photooxidative damage.

PURPOSE: Cellular or tissue reduction-oxidation (redox) is crucial in various diseases. The present study was conducted to analyze how tissue redox status is affected by photooxidative stress and whether the exogenous thiol antioxidant N-acetylcysteine (NAC) affects photooxidative stress-induced retinal damage. METHODS: Mice were intraperitoneally injected with either NAC (250 mg/kg) or phosphate-buffered saline (PBS) and exposed to white fluorescent light (8000 lux) for 2 hours. Levels of thioredoxin (TRX), glutaredoxin (GRX), and glutathione (GSH), endogenous regulators of redox; 4-hydroxy-2-nonenal (HNE)-modified protein, a marker of lipid peroxidation; and nuclear factor (NF)-kappaB, a redox-sensitive transcription factor in retinal samples, was measured by immunohistochemistry and Western blot or enzymatic recycling assay. Light-induced retinal damage estimated by electroretinography and quantitative immunohistochemistry for 8-hydroxy-2-deoxyguanosine (8OHdG index), a marker of oxidative stress-induced DNA damage, was compared in NAC- and PBS-treated mice. RESULTS: Upregulation of TRX and HNE-modified protein, decrease of GSH, and nuclear translocation of NF-kappaB were noted after light exposure in PBS-treated mice. These changes were suppressed in NAC-treated mice compared with PBS-treated mice. GRX was not upregulated after light exposure in any mice. The a- and b-wave amplitudes were significantly higher, and the 8OHdG index was significantly lower after light exposure in NAC-treated mice than in PBS-treated mice. CONCLUSIONS: Retinal redox status is altered by intense light and is normalized partially by the effect of NAC on TRX and GSH tissue levels. Manipulation of the tissue redox state by exogenous thiol replenishment may be a useful strategy to prevent retinal photooxidative damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2002

[Significance of the antioxidant factor, thioredoxin, in heart failure].

OBJECTIVES: Increases in oxidative stress may be involved in the progression of heart diseases. However, the serum levels of thioredoxin, a redox regulating protein, have been poorly investigated in patients with heart diseases. This study evaluated the clinical significance of the serum thioredoxin levels in patients with heart failure. METHODS: The serum thioredoxin levels were determined with a sandwich enzyme-linked immunosorbent assay in a total of 34 patients with dilated cardiomyopathy (n = 5), acute coronary syndrome (n = 7), and stable angina (n = 18), including effort angina (n = 7) and vasospastic angina (n = 11), and control subjects (n = 4). RESULTS: The serum thioredoxin levels were significantly elevated in patients with acute coronary syndrome (30.6 +/- 4.9 ng/ml, p < 0.001) and dilated cardiomyopathy (36.9 +/- 8.6 ng/ml, p < 0.001), but not in patients with stable angina (16.8 +/- 5.7 ng/ml, p = 0.27) compared with the control subjects (n = 4, 13.0 +/- 4.9 ng/ml). The serum thioredoxin level in patients with III and IV functional classes of the New York Heart Association (n = 8, 33.3 +/- 8.6 ng/ml, p < 0.001) was significantly higher than in the control subjects. In addition, the serum thioredoxin levels were negatively correlated with left ventricular ejection fractions of the patients (r = 0.59, p < 0.001). CONCLUSIONS: These results indicate a possible association between thioredoxin and the severity of heart failure.

Aged↗

PubMed2001

Mechanism of p53-dependent apoptosis induced by 3-methylcholanthrene: involvement of p53 phosphorylation and p38 MAPK.

Polycyclic aromatic hydrocarbons (PAHs) such as 3-methylcholanthrene (MC) cause untoward effects including carcinogenesis. Here we investigated the effect of MC on apoptosis. MC induced apoptosis, preceded by serine 15 phosphorylation and accumulation of p53. MC failed to cause apoptosis in p53-deficient MG63 cells, whereas ectopic expression of p53 in MG63 cells restored the response to MC. Therefore, MC-induced apoptosis was dependent on p53. MC also activated p38 mitogen-activated protein kinase (MAPK) at 16-24 h. Accumulation of p53 and p53 phosphorylated at serine 15 was not changed by SB203580, a specific inhibitor of p38 MAPK or overexpression of a dominant negative mutant of p38 MAPK at 8 h after MC treatment, whereas the accumulation was suppressed at 24 h. These results suggest that MC induces accumulation and phosphorylation of p53 via a p38 MAPK-independent (early) and p38 MAPK-dependent (late) pathway. SB203580 repressed MC-induced apoptosis. MC induced p38 MAPK activation in p53 expressing cells but not in p53-deficient cells, indicating that the p38 MAPK activation was dependent on early p53 activation. The current study shows that both p53 and p38 MAPK activation are required for MC-induced apoptosis and provides a novel model of a functional regulation between p53 and p38 MAPK in chemical stress-induced apoptosis.

Apoptosis↗

PubMedDate not supplied

Redox regulation of lung inflammation by thioredoxin.

The lungs are the richest in oxygen among the various organs of the body and are always subject to harmful reactive oxygen species. Regulation of the reduction/oxidation (redox) state is critical for cell viability, activation, proliferation, and organ functions. Although the protective importance of various antioxidants has been reported, few antioxidants have established their clinical usefulness. Thioredoxin (TRX), a key redox molecule, plays crucial roles as an antioxidant and a catalyst in protein disulfide/dithiol exchange. TRX also modulates intracellular signal transduction and exerts antiinflammatory effects in tissues. In addition to its beneficial effects in other organs, the protective effect of TRX in the lungs has been shown against ischemia/ reperfusion injury, influenza infection, bleomycin-induced injury, or lethal inflammation caused by interleukin- 2 and interleukin-18. Monitoring of TRX in the plasma, airway, or lung tissue may be useful for the diagnosis and follow-up of pulmonary inflammation. Promotion/modulation of the TRX system by the administration of recombinant TRX protein, induction of endogenous TRX, or gene therapies can be a therapeutic modality for oxidative stress-associated lung disorders.

Animals↗

PubMedDate not supplied

Overexpression of redox-active protein thioredoxin-1 prevents development of chronic pancreatitis in mice.

Chronic pancreatitis (CP) is considered to result from repetitive pancreatic injury, and sustained production of various proinflammatory cytokines and chemokines are closely involved in its pathogenesis. Monocyte chemoattractant protein 1 (MCP-1), a member of the CC chemokine family, is believed to contribute to the progression of CP through monocyte/macrophage recruitment. This study aimed to clarify the protective role of thioredoxin-1 (TRX-1), a redox-regulating protein with antioxidative activity, in MCP-1 production and pancreatic fibrosis using a CP model in transgenic mice overexpressing TRX-1 (TRX-1-TG mice) and wildtype C57BL/6 mice. Experimental CP was induced by repeated administration of cerulein and lipopolysaccharide for 6 weeks. In TRX-1-TG mice, pancreatic atrophy was ameliorated, and histologically detectable inflammatory cell infiltration, glandular atrophy, and pseudotubular complex formation were suppressed. Overexpression of TRX-1 also attenuated pancreatic fibrosis and suppressed the activation of pancreatic stellate cells. Serum levels of MCP-1 and pancreatic expression of transforming growth factor-beta, platelet-derived growth factor, and MCP-1 were reduced in TRX-1-TG mice compared with levels in wild-type mice. Overexpression of TRX-1 also reduced H(2)O(2)-induced MCP-1 production in isolated pancreatic acinar cells. These results indicate that TRX-1 can potentially attenuate pancreatic fibrosis via the suppression of oxidative stress and MCP-1-mediated chronic inflammation.

Actins↗

PubMedDate not supplied

Redox regulation of human thioredoxin network.

Oxidative stresses are largely mediated by intracellular protein oxidations by reactive oxygen species (ROS). Host cells are equipped with antioxidants that scavenge ROS. The cellular reduction/oxidation (redox) balance is maintained by ROS and antioxidants. Accumulating evidence suggests that the redox balance plays an important role in cellular signaling through the redox modification of cysteine residues in various important components of the signal transduction pathway. Thioredoxin (TRX) is a small protein playing important roles in cellular responses, including cell growth, cell cycle, gene expression, and apoptosis, to maintain the redox circumstance. Moreover, many recent papers have shown that the redox regulation by TRX is deeply involved in the pathogenesis of various oxidative stress-associated disorders. This review focuses on TRX and its related molecules, and discusses the role of TRX-dependent redox regulation in oxidative stress-induced signal transduction.

Humans↗

PubMedDate not supplied

Thioredoxin-1 suppresses systemic inflammatory responses against cigarette smoking.

Thioredoxin-1 (TRX) is a small redox-active protein with antioxidative effects and redox-regulating functions. Cigarette smoking is a major etiological factor in the pathogenesis of a variety of diseases and recruits systemic immune and inflammatory responses. This report demonstrates that TRX attenuates the systemic inflammatory responses induced by cigarette smoking. The mRNA expressions of tumor necrosis factor alpha (TNF-alpha) and macrophage migration inhibitory factor (MIF) were suppressed in the spleen of TRX overexpressing transgenic mice (TRX-tg) exposed to cigarette smoking, compared with control C57BL/6 mice. In addition, protein carbonylation, a marker of cellular protein oxidation, was enhanced by cigarette smoking in the tissues of heart and liver in control mice more than in TRX-tg mice. These findings suggest that TRX may suppress the systemic inflammatory responses against cigarette smoking.

Animals↗

PubMedDate not supplied

Redox regulation of stress signals: possible roles of dendritic stellate TRX producer cells (DST cell types).

Thioredoxin (TRX) is a 12 kDa protein with redox-active dithiol (Cys-Gly-Pro-Cys) in the active site. TRX is induced by a variety of stresses including viral infection and inflammation. The promoter sequences of the TRX gene contain a series of stress-responsive elements including ORE, ARE, XRE, CRE and SP-1. TRX promotes DNA binding of transcription factors such as NF-kappaB, AP-1 and p53. TRX interacts with target proteins modulating the activity of those proteins. We have identified TRX binding protein-2 (TBP-2), which was identical to vitamin D3 up-regulated protein 1 (VDUP1). Potential action of TBP-2/VDUP1 as a redox-sensitive tumor suppressor will be discussed. There is accumulating evidence for the involvement of TRX in the protection against infectious and inflammatory disorders. We will discuss the role of TRX-dependent redox regulation of the host defense mechanism, in particular its relation to the emerging concept of constitutive and/or inducible TRX on special cell types with dendritic and stellate morphology in the immune, endocrine and nervous systems, which we provisionally designate as dendritic stellate TRX producer cells (DST cell types).

Animals↗