Biomedical subjects

Junji Yodoi

Publications and source records attributed to Junji Yodoi.

At least 91 records · Page 5Linked to original sources

PubMed2003

Hepatitis C virus-associated tubulointerstitial injury.

BACKGROUND: Tubulointerstitial damage is recognized as a determinant of the prognosis of kidney disease. Various types of viral infection have been reported to induce tubulointerstitial lesions; however, that caused by hepatitis C virus (HCV) remains unclear, although glomerular lesions caused by this viral infection have been well documented. METHODS: To identify any association, we retrospectively investigated 320 patients who underwent renal biopsy and did not have extrarenal diseases causing tubulointerstitial nephritis. RESULTS: Of these patients, 13 patients had HCV infection and 307 patients did not. In a case-control study, HCV infection showed a significant association with the prevalence of tubulointerstitial injury. To offset the secondary tubulointerstitial change caused by advanced glomerulopathy, we performed a glomerular stage-matched comparison of patients with membranous nephropathy (MN). Nine patients with MN among the 13 HCV-infected patients and 18 HCV-negative patients with electron microscopic glomerular stage-matched MN were randomly selected from the overall pool of patients. Comparing areas of interstitial fibrosis and inflammatory cell infiltration, both were greater in HCV-infected than HCV-negative patients. In biopsy tissues from HCV-infected patients, positive signal for HCV was observed in the perinuclear area of tubular epithelial cells and infiltrating cells on immunohistochemistry and in situ hybridization. By a strand-specific reverse-transcription polymerase chain reaction for HCV, both genomic- and replicative-strand RNA were detected in renal tissues. CONCLUSION: These results suggest that HCV infection is a potent pathogenic factor of tubulointerstitial injury.

Adolescent↗

PubMed2003

Modulation of glutathione and thioredoxin systems by calorie restriction during the aging process.

Accumulating evidence strongly suggests that oxidative stress underlies aging processes and that calorie restriction (CR) retards aging processes, leading to an extended lifespan for various organisms. Recent studies revealed that the anti-aging action of CR depends on its anti-oxidative mechanism. However, at present, the status of glutathione (GSH) and thioredoxin (Trx) system, two major thiol redox systems in animal cells during aging and its modulation by CR has not fully been explored. The purpose of this study is two-fold: one, to determine whether these two systems in rat kidney are altered as a consequence of aging; two, to determine whether these systems can be modulated by anti-oxidative CR. The results of our study showed that GSH and GSH-related enzyme activities decreased with age in ad libitum (AL)-fed rats, while CR rats consistently showed resistance to decreases in these activities. Data from the present data further showed that while Trx and Trx reductase (TrxR) in cytoplasm decrease with age in AL-fed rats, CR prevents these decreases. In contrast, we also found that the nuclear translocation of the redox regulators, Trx and Ref-1, increase with age, which was suppressed in CR rats. Therefore, increases in nuclear Trx and Ref-1 during aging may result in the up-regulation of redox-sensitive transcription factors, such as NF-kappaB or AP-1, via the interaction of Ref-1 and Trx in a redox-dependent manner. Our conclusion is that a redox imbalance occurs during aging and that redox changes are minimized through the anti-oxidative action of CR.

Aging↗

PubMed2003

Temocapril treatment ameliorates autoimmune myocarditis associated with enhanced cardiomyocyte thioredoxin expression.

Thioredoxin (TRX) is a redox regulatory protein that protects cells from various stresses. Angiotensin-converting enzyme (ACE) inhibitor was reported to enhance endogenous antioxidant enzyme activities. This study was carried out to investigate whether temocapril, a novel non-sulfhydryl containing ACE inhibitor, reduces the severity of myocarditis via redox regulation mechanisms involving TRX. Western blot showed that temocapril enhanced cytosolic redox regulatory protein TRX expression, but neither mitochondrial TRX2 nor antioxidant enzymes, such as copper-zinc superoxide dismutase (Cu/Zn-SOD) or manganese superoxide dismutase (Mn-SOD) expression, was increased by the preconditioning treatment. In rats with experimental autoimmune myocarditis (EAM), the protein carbonyl content, a marker of cellular protein oxidation, was increased accompanied with enhanced TRX expression. An immunohistochemical study showed that TRX stain was enhanced in infiltrating inflammatory cells and in damaged myocytes. The severity of the myocarditis and the protein carbonyl contents were less increased in temocapril treatment (10 mg/kg/day, orally) from day 1 to day 21 in which TRX was up regulated when the inflammation started, but not in temocapril treatment from day 15-21 in which TRX was not up-regulated when the inflammation started. The results suggest that TRX and the redox state modified by TRX may play a crucial role in the pathophysiology of EAM. Temocapril ameliorates myocarditis associated with inducing TRX increase in a preconditioning manner, although the mechanism of TRX induction by temocapril remains to be elucidated.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

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

BACKGROUND: Thioredoxin (TRX) is a small protein with redox-regulating functions. Although TRX is known to be induced in response to various forms of oxidative stress, including ischemia/reperfusion injury, the induction and the specific role of this protein in the kidney have not been fully investigated. METHODS: Renal ischemia/reperfusion was induced by the clipping and release of renal arteries in C57BL/6 and human thioredoxin-overexpressing transgenic (hTRX-Tg) mice. TRX protein was detected by immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). TRX mRNA was detected by in situ hybridization and Northern blotting. Renal functions were evaluated by measuring the levels of blood urea nitrogen and serum creatinine in these mice. RESULTS: With ischemia/reperfusion, endogenous murine TRX was rapidly depleted from the cytosol in the cortical proximal tubuli and detected in the urinary lumen, whereas it was spread diffusely in all segments of the tubular epithelial cells in sham-operated mice. The urinary excretion of TRX increased transiently after ischemia/reperfusion and recovered to the control level in 72 hours. In the medullary thick ascending limb (mTAL), however, TRX was specifically retained in the cytosol. A similar distribution change of transgenic hTRX was observed in the kidney of hTRX-Tg. These hTRX-Tg mice were more resistant to the injury to the mTAL and functional deterioration caused by ischemia/reperfusion, compared with wild-type mice. CONCLUSION: 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.

Animals↗

PubMed2003

Elevation of blood thioredoxin in hemodialysis patients with hepatitis C virus infection.

BACKGROUND: Thioredoxin (TRX) is a stress-inducible thiol-containing protein, which has been shown to be an indicator of oxidative stress in a variety of diseases. The association between oxidative stress and hepatitis C virus (HCV) infection, however, remains unknown in hemodialysis patients. METHODS: We measured serum TRX levels in 85 hemodialysis patients positive for anti-HCV antibodies (age, 60 +/- 1 years old; hemodialysis duration, 17 +/- 1 years; M/F = 57/28) by enzyme-linked immunosorbent assay (ELISA), and examined whether blood TRX may be associated with HCV-related hepatic injury. RESULTS: Serum TRX was significantly higher in hemodialysis patients with HCV infection (112.3 +/- 3.7 ng/mL, N = 85) than in those without HCV infection (69.7 +/- 3.3 ng/mL, N = 59) (age, 69 +/- 2 years old; hemodialysis duration, 6 +/- 1 years; M/F = 32/27, P < 0.01) or normal subjects (28.0 +/- 5.4 ng/mL, N = 9). TRX was significantly correlated with time on hemodialysis (r = 0.27, P = 0.01) in HCV-positive patients, while it was associated with the patient's age in HCV-negative patients (r = 0.42, P < 0.01). Blood TRX was significantly correlated with asparate aminotransferase in patients with HCV infection (r = 0.34, P < 0.01) and without HCV infection (r = 0.46, P < 0.01). However, serum TRX was not associated with blood alanine aminotransferase, a relatively specific marker of hepatic cellular damage, in HCV-infected hemodialysis patients. A significant relationship was found between serum ferritin and TRX (r = 0.25, P = 0.02) and malondialdehyde (MDA) values (r = 0.25, P = 002) in HCV-positive patients. Serum TRX was also higher in the patients receiving weekly iron supplement with HCV infection (135.3 +/- 10.2 ng/mL vs. 110.2 +/- 3.9 ng/mL, P = 0.06) and without HCV infection (91.8 +/- 12.1 ng/mL vs. 65.2 +/- 2.7 ng/mL, P < 0.01). CONCLUSION: There was a greater increase in serum TRX in hemodialysis patients with HCV viremia than without HCV viremia. However, there may not be an association between serum TRX and HCV-related hepatic injury. TRX increased with serum ferritin in HCV-infected patients and further increased by iron infusion. These findings indicate that HCV infection and iron loading may aggravate oxidative stress in dialysis patients.

Aged↗

PubMed2003

Overexpression of thioredoxin prevents acute hepatitis caused by thioacetamide or lipopolysaccharide in mice.

Thioredoxin (Trx) is a small redox-active protein with antioxidant and antiapoptotic effects. Trx transgenic (Tg) mice are more resistant to cerebral infarction and survive longer than wild-type (WT) C57BL/6 mice. The aim of the present study was to investigate the protective role of Trx in acute hepatitis models. The expression of endogenous Trx was decreased in thioacetamide (TAA)-induced acute hepatitis. TAA (100 microg/g) was injected intraperitoneally in WT and Tg mice. Survival rate after TAA injection was higher in Tg mice than in WT mice. The level of oxidative stress was significantly less in Tg mice than in WT mice, as shown by the protein carbonylation assay and lipid peroxidation assay. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells were less in Tg mice than in WT mice, which was consistent with DNA laddering assay. Caspase-3 and caspase-9 activities and cytochrome c release were significantly inhibited in Tg mice compared with those in WT mice. In addition, lipopolysaccharide (LPS) plus d-galactosamine (GalN), or anti-Fas antibody (Jo2) were injected. Survival rate after LPS plus GalN injection was much higher in Tg mice than in WT mice. In contrast, there was no difference in survival rate after Jo2 injection between WT and Tg mice. In conclusion, transgene of Trx attenuated TAA- or LPS-induced acute lethal hepatitis. In addition to an antioxidant effect, Trx has the potential to protect acute liver injury via an antiapoptotic effect, which mainly inhibits mitochondria-mediated apoptosis signaling.

Acute Disease↗

PubMed2003

Effect of vitamin E on serum aminotransferase and thioredoxin levels in patients with viral hepatitis C.

OBJECTIVES: Oxidative stress induces cellular responses such as cell death, gene activation and cell proliferation, in the liver. Vitamin E (Vit. E) has been found to protect the liver against oxidative stress in animal experiments. Thioredoxin (TRX) is a stress inducible, multifunctional protein, secreted during oxidative stress. This study evaluated effects of Vit. E on serum TRX and aminotransferase levels in hepatitis C virus (HCV) patients, partly non-responsive to initial interferon (IFN), with higher than average level of serum alanine aminotransferase (ALT) after receiving anti-inflammatory drug treatment. METHODS: Seventeen HCV patients (male = 3; female = 14) of age 62 +/- 7.65 years receiving anti-inflammatory drug therapy, at least 6 months prior to Vit. E administration, were given d-alpha-tocopherol 500 mg/day, orally, for a period of 3 months. ALT, aspartate aminotransferase (AST), TRX and Vit. E were measured at 0, 1, 2 and 3 months and 1 month after end of treatment. As controls, the same patients biochemical data, 3 months from the start of therapy were used. Patients were divided into three categories: total patients "T", low ALT group "L" (ALT < 70 IU/l) and high ALT group "H" (ALT > 70 IU/l), respectively. RESULTS: The ALT level was lowered, significantly in group H, in the 1st, 2nd, 3rd and 1-month post therapy, compared to the initial value. But group L showed little or no change in ALT. Post Vit. E therapy, in groups T and H, the TRX level was elevated but remained below initial levels, whereas in group L, TRX level remained significantly lower than the pretreatment value. Groups T and L, showed significant reduction (p < 0.05) in serum TRX levels in the 2nd and 3rd month. Group H showed a tendency towards TRX reduction, but not significantly. Serum Vit. E levels increased significantly (p < 0.0001) from the 1st to 3rd month in all three T, H and L groups. CONCLUSION: Oxidative stress induced liver damage is reduced by Vit. E in patients with viral hepatitis C, particularly those with initial ALT levels > 70 IU/l. Vit. E treatment causes reduction of oxidative stress markers as TRX and ALT in sera. Therefore, Vit. E can act as a supportive therapy to combat liver damage caused by oxidative stress, in such patients with continuously high levels of ALT even after anti-viral and anti-inflammatory drug therapy.

Aged↗

PubMed2003

The role of thioredoxin in the aging process: involvement of oxidative stress.

Reactive oxygen species are produced by various stressors derived from internal and external sources, including endogenous metabolic activities. Glucose metabolism is one of the most primitive sources for energy production for most cells; however, it may at the same time yield hazardous oxidative stress via simultaneous oxidant production. The protective mechanism against oxidative stress is thus an indispensable biological function. Recently, genetic mutation loci affecting life span were isolated from experimental model organisms, and several locus products were found to be closely linked with machinery either producing or defending oxidative stress. Thioredoxin (TRX) is a small protein having strong antioxiradical quenching capabilities and other multiple functions depending on the cellular redox state. In this review, we focus on the role of TRX in the aging process (senescence) as a redox-regulating molecule against oxidative stress. We also discuss the possibility of the TRX system serving as an index marker for cellular proliferation and senescence.

Aging↗

PubMed2003

Redox regulation by thioredoxin in cardiovascular diseases.

Increasing evidence has indicated that the modulation of intracellular redox states has important aspects to cellular events, such as cellular proliferation, activation, growth inhibition, or death via the regulation of intracellular signal transduction and gene expression. Thioredoxin (TRX) is a multifunctional stress-inducible protein, which protects cells from various types of stresses. TRX has not only a scavenging activity of reactive oxygen species, but also a regulating activity of various intracellular molecules including transcription factors. We demonstrated that the serum TRX levels are correlated with the severity of heart failure, and are negatively correlated with left ventricular ejection fractions of patients with heart failure. The expression of TRX is enhanced in endothelial cells and macrophages in human atherosclerotic plaques, in balloon-injured rat arteries, and in damaged cardiomyocytes of rats with acute myocarditis. Overexpression of TRX in transgenic mice attenuates adriamycin-induced cardiotoxicity by reducing oxidative stresses. These findings suggest that TRX and the redox system modulated by TRX have an important role in cellular defense against oxidative stress in cardiovascular diseases.

Animals↗

PubMed2003

Cutaneous arteriolar thioredoxin expression in patients with heart failure.

Cutaneous microangiopathic lesions exist in patients with heart failure, and heart failure is associated with increased oxidative stress. Thioredoxin (TRX) is stress-inducible and has a cytoprotective effect against oxidative stress. Accordingly, to investigate whether arteriolar TRX expression was increased in the skin of patients with congestive heart failure (CHF), skin biopsies were taken at the time of cardiac catheterization, and the results were compared with those of control subjects. The diagnosis of CHF was done by cardiac catheterization with reference to elevated plasma concentrations of TRX and brain natriuretic peptide (BNP). Increased TRX expression was found in the skin biopsies of 29 of the 35 patients with CHF, but in none of the 8 control subjects; the semiquantitative grade of arteriolar TRX immunoreactivity was 2.5+/-1.0 in patients with CHF and 1.0+/-0.0 in controls, respectively (p<0.01). The severity of arteriolar TRX expression did not correlate with the New York Heart Association functional class. These results indicate that cutaneous arteriolar TRX expression in patients with CHF may reflect the excessive oxidative stress of the peripheral circulation associated with the condition.

Aged↗

PubMed2003

Redox regulation of cell growth and cell death.

Oxidative stress evokes various cellular events, including activation of transcription factors, apoptosis, and cell cycle arrest. Accumulating evidence shows that reduction/oxidation (redox) plays an important role in the regulation of apoptosis and cell cycle arrest elicited by oxidative stress. Cellular redox is controlled by the thioredoxin (TRX) and glutathione (GSH) systems. TRX and GSH systems regulate cell growth and cell death by the activation of transcription factors, the sensitivity of cells to cytokines and growth factors, and the components of the apoptosis pathways. This brief review describes the current knowledge on the redox regulation of cell growth and apoptosis.

Animals↗

PubMed2003

[Temocapril treatment upregulated cardiomyocyte thioredoxin expression and improved autoimmune myocarditis].

OBJECTIVE: Thioredoxin (TRX) is a redox regulatory protein that protects cells from various stresses. Angiotensin-converting enzyme (ACE) inhibitor was reported to enhance endogenous antioxidant enzyme activities. This study was carried out to investigate whether temocapril, a novel non-sulfhydryl containing ACE inhibitor, reduces the severity of myocarditis via redox regulation mechanisms involving TRX. METHODS: The up-regulation of TRX by temocapril treatment was checked by Western blot in normal rat myocytes in vitro and in vivo, as well as in rats with experimental autoimmune myocarditis (EAM). RESULTS: Temocapril enhanced cytosolic redox regulatory protein TRX expression, but neither mitochondrial TRX2 nor antioxidant enzymes, such as copper-zinc superoxide dismutase (Cu/Zn-SOD) or manganese superoxide dismutase (Mn-SOD) expression, was up-regulated by the preconditioning treatment. In rats with EAM, the severity of myocarditis and the protein carbonyl contents were less increased in temocapril treatment (10 mg x kg(-1) x d(-1), orally) from day 1 to day 21, but not in temocapril treatment from day 15 to day 21. If the characteristics of this model that myocardial inflammation begins around day 15 and keeps on until day 21 is considered, temocapril treatment for 3 weeks might be thought as a preconditioning treatment. CONCLUSIONS: TRX and the redox state modified by TRX may play a crucial role in the pathophysiology of EAM. Temocapril ameliorates myocarditis with inducing TRX up-regulation in a preconditioning manner, although the mechanism of TRX up-regulation by temocapril remains to be elucidated.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Thioredoxin reductase regulates AP-1 activity as well as thioredoxin nuclear localization via active cysteines in response to ionizing radiation.

A recently identified class of signaling factors uses critical cysteine motif(s) that act as redox-sensitive 'sulfhydryl switches' to reversibly modulate specific signal transduction cascades regulating downstream proteins with similar redox-sensitive sites. For example, signaling factors such as redox factor-1 (Ref-1) and transcription factors such as the AP-1 complex both contain redox-sensitive cysteine motifs that regulate activity in response to oxidative stress. The mammalian thioredoxin reductase-1 (TR) is an oxidoreductase selenocysteine-containing flavoprotein that also appears to regulate multiple downstream intracellular redox-sensitive proteins. Since ionizing radiation (IR) induces oxidative stress as well as increases AP-1 DNA-binding activity via the activation of Ref-1, the potential roles of TR and thioredoxin (TRX) in the regulation of AP-1 activity in response to IR were investigated. Permanently transfected cell lines that overexpress wild type TR demonstrated constitutive increases in AP-1 DNA-binding activity as well as AP-1-dependent reporter gene expression, relative to vector control cells. In contrast, permanently transfected cell lines expressing a TR gene with the active site cysteine motif deleted were unable to induce AP-1 activity or reporter gene expression in response to IR. Transient genetic overexpression of either the TR wild type or dominant-negative genes demonstrated similar results using a transient assay system. One mechanism through which TR regulates AP-1 activity appears to involve TRX sub-cellular localization, with no change in the total TRX content of the cell. These results identify a novel function of the TR enzyme as a signaling factor in the regulation of AP-1 activity via a cysteine motif located in the protein.

Cysteine↗

PubMed2002

Overexpression of thioredoxin-1 in transgenic mice attenuates adriamycin-induced cardiotoxicity.

BACKGROUND: Adriamycin (ADR) is an anticancer drug known to cause severe cardiac toxicity by generating free radicals. We investigated the role of a redox-regulating molecule, thioredoxin-1 (TRX1), in ADR-induced cardiotoxicity. METHODS AND RESULTS: The in vitro study showed that TRX1 was dose-dependently increased concomitant with the formation of hydroxyl radicals in ADR-treated neonatal rat cardiomyocytes. Lactate dehydrogenase-releasing assay showed that treatment with recombinant human TRX1 suppressed cardiomyocyte injury in ADR-treated cardiomyocytes. To examine the biological significance of TRX1 in vivo, we used transgenic mice expressing increased levels of human TRX1 (TRX1-TG mice). Electron microscopy revealed that mitochondria, myofibrils, and other cellular details were much better maintained in ADR-treated TRX1-TG mice than in ADR-treated nontransgenic (WT) mice. The increase in the protein carbonyl content, a marker of cellular protein oxidation, was suppressed in ADR-treated TRX1-TG mice compared with ADR-treated WT mice. The formation of hydroxyl radicals in ADR-treated heart homogenates of TRX1-TG mice was decreased compared with WT mice. For the survival study, all WT mice treated with ADR died within 6 weeks, but 5 of 6 TRX1-TG mice treated with ADR survived >8 weeks. CONCLUSIONS: TRX1 is upregulated by intracellular oxidative stress generated by ADR. TRX1 has a protective role against ADR-induced cardiotoxicity by reducing oxidative stress.

Animals↗

PubMed2002

A comparative study on the hydroperoxide and thiol specificity of the glutathione peroxidase family and selenoprotein P.

Glutathione peroxidase catalyzes the reduction of hydrogen peroxide and organic hydroperoxide by glutathione and functions in the protection of cells against oxidative damage. Glutathione peroxidase exists in several forms that differ in their primary structure and localization. We have also shown that selenoprotein P exhibits a glutathione peroxidase-like activity (Saito, Y., Hayashi, T., Tanaka, A., Watanabe, Y., Suzuki, M., Saito, E., and Takahashi, K. (1999) J. Biol. Chem. 274, 2866-2871). To understand the physiological significance of the diversity among these enzymes, a comparative study on the peroxide substrate specificity of three types of ubiquitous glutathione peroxidase (cellular glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, and extracellular glutathione peroxidase) and of selenoprotein P purified from human origins was done. The specific activities and kinetic parameters against two hydroperoxides (hydrogen peroxide and phosphatidylcholine hydroperoxide) were determined. We next examined the thiol specificity and found that thioredoxin is the preferred electron donor for selenoprotein P. These four enzymes exhibit different peroxide and thiol specificities and collaborate to protect biological molecules from oxidative stress both inside and outside the cells.

Glutathione Peroxidase↗

PubMed2002

Temocapril treatment ameliorates autoimmune myocarditis associated with enhanced cardiomyocyte thioredoxin expression.

OBJECTIVE: Thioredoxin (TRX) is a redox regulatory protein that protects cells from various stresses. Angiotensin-converting enzyme (ACE) inhibitor was reported to enhance endogenous antioxidant enzyme activities. This study was carried out to investigate whether temocapril, a novel non-sulfhydryl-containing ACE inhibitor, reduces the severity of myocarditis via redox regulation mechanisms involving TRX. METHODS AND RESULTS: In normal rat myocytes in vitro and in vivo, Western blot showed that temocapril enhanced cytosolic redox regulatory protein TRX expression, but that neither mitochondrial TRX2 nor antioxidant enzymes, such as copper-zinc superoxide dismutase (Cu/Zn-SOD) or manganese superoxide dismutase (Mn-SOD) expression, was up-regulated by the preconditioning treatment. In rats with experimental autoimmune myocarditis (EAM), the severity of myocarditis and the protein carbonyl contents were less increased in temocapril treatment (10 mg/kg/day, orally) from day 1 to day 21, but not in temocapril treatment from day 15 to day 21. An immunohistochemical study showed that TRX stain was enhanced in infiltrating inflammatory cells and in damaged myocytes. Considering the characteristics of this model that myocardial inflammation begins around day 15 and increases until day 21, temocapril treatment for 3 weeks might be thought of as a preconditioning treatment. CONCLUSIONS: The results suggest that TRX and the redox state modified by TRX may play a crucial role in the pathophysiology of EAM. Temocapril ameliorates myocarditis associated with inducing TRX up-regulation in a preconditioning manner, although the mechanism of TRX up-regulation by temocapril remains to be elucidated.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

C-propeptide region of human pro alpha 1 type 1 collagen interacts with thioredoxin.

Thioredoxin (TRX) is one of major components of thiol reducing systems. To investigate the molecular mechanism of TRX function in the lung tissue, we screened a human lung epithelial cell cDNA library for TRX-binding protein by yeast two-hybrid systems. We isolated a plasmid containing C-propeptide region of human pro alpha 1 type 1 collagen (CP-pro alpha 1(1)). CP-pro alpha 1(1) stably binds to wild type TRX but not to mutant TRX, in which redox-active cysteine residues are substituted. Failure of the interaction of mutant TRX with CP-pro alpha 1(1) was confirmed in yeast two-hybrid systems. The CP-pro alpha 1(1)/TRX interaction was increased by dithiothreitol treatment, but was markedly inhibited by hydrogen peroxide or diamide treatment. These data showed that the reducing status of TRX active site cysteine residues is important for the TRX-CP-pro alpha 1(1) interaction, indicating that collagen biosynthesis is under the regulation of TRX-dependent redox control.

Binding Sites↗

PubMed2002

Attenuation of retinal photooxidative damage in thioredoxin transgenic mice.

Thioredoxin (TRX) is an endogenous redox (reduction/oxidation) regulator that has cytoprotective effects against various types of oxidative stresses. Exposure to excessive levels of white light induces retinal photoreceptor damage. To test the cytoprotective effect of overexpressed TRX against retinal photooxidative damage, both TRX transgenic (trx-tg) mice and C57BL/6 (wild type) mice were exposed to intense white fluorescent light. The amounts of oxidized and tyrosine-phosphorylated proteins decreased in the neural retinas of the trx-tg mice compared to the wild type mice after light exposure. The electroretinographic amplitudes were higher and the formation of oxidized DNA was lower in trx-tg mice compared to wild type mice after light exposure. These results suggest that overexpression of TRX suppresses retinal photooxidative damage. TRX intensification may be a useful therapeutic strategy to prevent retinal photic injury.

Animals↗