Biomedical subjects

Junji Yodoi

Publications and source records attributed to Junji Yodoi.

At least 37 records · Page 2Linked to original sources

PubMed2005

Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis.

Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of kappaB-alpha, thereby suppressing proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.

Acute Disease↗

PubMed2005

High thioredoxin expression is associated with resistance to docetaxel in primary breast cancer.

PURPOSE: Thioredoxin overexpression is suggested to be associated with resistance to several chemotherapeutic agents in vitro. In the present study, it has been studied whether or not high thioredoxin expression is associated with resistance to docetaxel therapy in breast cancer patients. PATIENTS AND METHODS: Sixty-three primary breast cancer patients were treated with docetaxel (60 mg/m(2), q3w) for four cycles in the neoadjuvant setting. Expression of thioredoxin, estrogen receptor (ER), p53, BRCA-1, and Bcl-2 in tumor tissues obtained before docetaxel therapy was studied by immunohistochemistry (thioredoxin, p53, BRCA-1, and Bcl-2) and enzyme immunoassay (ER), and relationship of expression of these biomarkers with a pathologic response was investigated. RESULTS: There was no significant correlation between the expression of p53, BRCA-1, or Bcl-2 and a response to docetaxel. However, tumors with high thioredoxin expression showed a significantly lower response rate (0%) than those with low thioredoxin expression (30.6%; P = 0.018) and ER-negative tumors showed a significantly higher response rate (32.4%) than ER-positive tumors (10.7%; P = 0.043). Thioredoxin expression significantly increased after docetaxel therapy (mean, 56.1%) as compared with that before docetaxel therapy (mean, 28.6%; P < 0.0001) but there was no significant association between the extent of increase in thioredoxin expression and response. CONCLUSION: High thioredoxin expression in prechemotherapy tumor samples, but not the increase in thioredoxin expression induced by docetaxel, is associated with resistance to docetaxel in breast cancer. Thioredoxin and ER might be clinically useful in the prediction of a response to docetaxel.

Antineoplastic Agents, Phytogenic↗

PubMed2005

Thioredoxin-binding protein-2-like inducible membrane protein is a novel vitamin D3 and peroxisome proliferator-activated receptor (PPAR)gamma ligand target protein that regulates PPARgamma signaling.

Thioredoxin binding protein-2 (TBP-2), which is identical with vitamin D3 (VD3) up-regulated protein 1 (VDUP1), plays a crucial role in the integration of glucose and lipid metabolism. There are three highly homologous genes of TBP-2/vitamin D3 up-regulated protein 1 in humans, but their functions remain unclear. Here we characterized a TBP-2 homolog, TBP-2-like inducible membrane protein (TLIMP). In contrast to TBP-2, TLIMP displayed no significant binding affinity for thioredoxin. TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome- and lysosome-associated functions. VD3 and ligands of peroxisome proliferator-activated receptor (PPAR)-gamma, an important regulator of energy metabolism and cell growth inhibition, induced the expression of TLIMP as well as TBP-2. Overexpression of TLIMP suppressed both anchorage-dependent and -independent cell growth and PPARgamma ligand-inducible gene activation. These results suggest that TLIMP, a novel VD3- or PPARgamma ligand-inducible membrane-associated protein, plays a regulatory role in cell proliferation and PPARgamma activation.

Amino Acid Sequence↗

PubMed2005

Impaired fatty acid utilization in thioredoxin binding protein-2 (TBP-2)-deficient mice: a unique animal model of Reye syndrome.

Thioredoxin binding protein-2 (TBP-2) is a negative regulator of thioredoxin and has multiple regulatory functions in cellular redox, growth, differentiation, apoptosis, and aging. To investigate the function of TBP-2 in vivo, we generated mice with targeted inactivation of TBP-2 (TBP-2-/- mice). Here, we show that TBP-2 expression is markedly up-regulated during fasting in wild-type mice, while TBP-2-/- mice were predisposed to death with bleeding tendency, as well as hepatic and renal dysfunction as a result of 48 h of fasting. The fasting-induced death was rescued by supplementation of glucose but not by that of oleic acid, suggesting that inability of fatty acid utilization plays an important role in the anomaly of TBP-2-/- mice. In these mice, plasma free fatty acids levels are higher, whereas glucose levels are lower than those of wild-type mice. Compared with wild-type mice, TBP-2-/- mice showed increased levels of plasma ketone bodies, pyruvate and lactate, indicating that Krebs cycle-mediated fatty acid utilization is impaired. Because the fatal impairment of fatty acid utilization is a characteristically metabolic feature of Reye (-like) syndrome, TBP-2-/- mouse may represent a novel model for investigating the pathophysiology of these disorders.

Acetyl Coenzyme A↗

PubMed2005

Thioredoxin suppresses airway hyperresponsiveness and airway inflammation in asthma.

Thioredoxin (TRX) is a 12-kDa redox (reduction/oxidation)-active protein that has a highly conserved site (-Cys-Gly-Pro-Cys-) and scavenges reactive oxygen species. Here we examined whether exogenously administered TRX modulated airway hyperresponsiveness (AHR) and airway inflammation in a mouse asthma model. Increased AHR to inhaled acetylcholine and airway inflammation accompanied by eosinophilia were observed in OVA-sensitized mice. Administration of wild-type but not 32S/35S mutant TRX strongly suppressed AHR and airway inflammation, and upregulated expression of mRNA of several cytokines (e.g., IL-1alpha, IL-1beta, IL-1 receptor antagonist, and IL-18) in the lungs of OVA-sensitized mice. In contrast, TRX treatment at the time of OVA sensitization did not improve AHR or airway inflammation in OVA-sensitized mice. Thus, TRX inhibited the asthmatic response after sensitization, but did not prevent sensitization itself. TRX and redox-active protein may have clinical benefits in patients with asthma.

Animals↗

PubMed2005

Thioredoxin-1 suppresses lung injury and apoptosis induced by diesel exhaust particles (DEP) by scavenging reactive oxygen species and by inhibiting DEP-induced downregulation of Akt.

Diesel exhaust particles (DEP) are reactive oxygen species (ROS)-inducing toxic agents that damage lungs. Thioredoxin-1 (Trx-1) is a thiol protein with antioxidant and redox-regulating effects. In this study, we demonstrate that Trx-1 scavenges ROS generated by DEP and attenuates the lung injury. Intratracheal instillation of DEP resulted in the generation of more hydroxyl radicals in control mice than in human Trx-1 (hTrx-1)-transgenic mice as measured by noninvasive L-band in vivo electron spin resonance. DEP caused acute lung damage with massive infiltration of inflammatory cells in control mice, but much less damage in hTrx-1-transgenic mice. The hTrx-1 transgene protected the mice against DEP toxicity. To investigate further the molecular mechanism of the protective role of Trx-1 against DEP-induced lung injury, we used hTrx-1-transfected L-929 cells and recombinant hTrx-1 (rhTrx-1)-pretreated A-549 cells. DEP-induced ROS generation was suppressed by hTrx-1 transfection or pretreatment with rhTrx-1. Endogenous Trx-1 expression was induced by DEP in control cells. The downregulation of Akt phosphorylation by DEP resulted in apoptosis, which was prevented by Trx-1. Moreover, an Akt inhibitor canceled this protective effect of Trx-1. Collectively, the results suggest that Trx-1 exerts antioxidant effects in vivo and in vitro and that this plays a role in protection against DEP-induced lung damage by regulating Akt-mediated antiapoptotic signaling.

Animals↗

PubMed2005

Redox regulation of the signaling pathways leading to eNOS phosphorylation.

Oxidative stress mediates positive and negative effects on physiological processes. Recent reports show that H(2)O(2) induces phosphorylation and activation of endothelial nitric oxide synthase (eNOS) through an Akt-phosphorylation-dependent pathway. In this study, we assessed activation of eNOS and Akt by determining their phosphorylation status. Whereas moderate levels of H(2)O(2) (100 microM) activated the Akt/eNOS pathway, higher levels (500 microM) did not, suggesting differential effects by differing levels of oxidative stress. We then found that two pro-oxidants with activity on sulfhydryl groups, 1-chloro-2,4-dinitrobenzene (CDNB) and diethyl maleate (DEM), blocked the phosphorylation events induced by 100 microM H(2)O(2). GSH was not a target thiol in this system because buthionine sulfoximine did not inhibit this phosphorylation. However, down-regulation of cell membrane surface and intracellular free thiols was associated with the inhibition of phosphorylation, suggesting that oxidation of non-GSH thiols inhibits the H(2)O(2)-induced phosphorylation of eNOS and Akt. DTT reversed the inhibitory effects of CDNB and DEM on Akt phosphorylation and concomitantly restored cell surface thiol levels more efficiently than it restored intracellular thiols, suggesting a more prominent role for the former. Similarly, DEM and CDNB inhibited TNF-alpha-induced Akt and eNOS phosphorylation, suggesting that thiol modification is involved in eNOS inductive pathways. Our findings suggest that eNOS activation is exquisitely sensitive to regulation by redox and that cell surface thiols, other than glutathione, regulate signal transduction leading to phosphorylation of Akt and eNOS.

Animals↗

PubMed2005

Plasma thioredoxin levels in patients with unstable angina.

Plasma levels of human thioredoxin are indicative of the responses against oxidative stress. We measured the plasma thioredoxin levels in patients with unstable angina in order to examine the relationships between subsequent clinical course and plasma thioredoxin levels before and after treatment for unstable angina. Blood was sampled both on admission and after treatment in 44 patients with unstable angina. In addition, blood samples were obtained from 41 patients with stable exertional angina and 41 patients with chest pain syndrome after admission. The plasma levels of thioredoxin were the highest in the unstable angina group among three groups (p<0.001). Treatment of unstable angina decreased the plasma thioredoxin levels (p<0.01). We divided the patients with unstable angina into two groups according to the plasma thioredoxin levels on admission and after treatment. There was a significant difference in Braunwald's classification between the high thioredoxin and the low thioredoxin group on admission, as analyzed by the chi2 test with Yates's correction (p<0.05). Moreover, there was a significant difference in incidence of recurrent anginal attacks at rest between the high thioredoxin and the low thioredoxin group after treatment, as analyzed by the chi2 test with Yates's correction (p<0.001). The present study demonstrated that plasma thioredoxin levels are significantly increased in patients with unstable angina compared to those with stable exertional angina and chest pain syndrome. Thioredoxin levels were associated with recurrent myocardial ischemia in patients with unstable angina.

Aged↗

PubMed2005

Selective neuronal vulnerability and inadequate stress response in superoxide dismutase mutant mice.

To understand the role of oxidative stress and mitochondrial defects in the development of neurodegeneration, we examined the age-related pathological changes and corresponding gene expression profiles in homozygous mutant mice deficient in the mitochondrial form of superoxide dismutase (MnSOD, SOD2). These Sod2-/- mice, generated on a B6D2F1 background, developed ataxia at Postnatal Day (P) 11 and progressively deteriorated with frequent seizures by P14. Histopathological examination revealed neurodegenerative changes consistent with the neurological signs. Vacuolar degeneration was observed in neurons and neuropil throughout the brainstem and rostral cortex. The motor trigeminal nucleus in brainstem and the deeper layers of the motor cortex were the earliest regions to degenerate, with the thalamus and hippocampus affected at later stages. Oligonucleotide microarrays were used to compare gene expression profiles in the brainstem and thalamus of Sod2+/+ and -/- mice from birth to P18. Notably, a large set of heat-shock protein genes was transcriptionally down regulated, and this was most likely due to a reduction in the heat-shock transcription factor 1 (HSF1). Other major classes of differentially expressed genes include lipid biosynthesis and ROS metabolism.

Amino Acid Motifs↗

PubMed2005

Cytoprotective effects of geranylgeranylacetone against retinal photooxidative damage.

Exposure to excessive light induces retinal photoreceptor cell damage, leading to development and progression of various retinal diseases. We tested the effect of geranylgeranylacetone (GGA), an acyclic polyisoprenoid, on light-induced retinal damage in mice. Oral treatment with GGA (1.0 mg/d) for 5 d induced thioredoxin (Trx) and heat shock protein 72 (Hsp72) predominantly in the retinal pigment epithelium (RPE). After white light exposure (8000 lux for 2 h), the percentage of terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive photoreceptor cells decreased significantly at 24 and 96 h, and the number of photoreceptor cell nuclei at 96 h and the electroretinographic amplitudes of the a- and b-waves at 4 and 10 d increased significantly in GGA-pretreated mice compared with saline-pretreated mice. Light-induced upregulations of 8-hydroxy-2-deoxyguanosine and 4-hydroxy-2-nonenal-modified protein, markers of oxidative stress, were inhibited by GGA pretreatment. To elucidate the cytoprotective mechanism of GGA and Trx, we used human K-1034 RPE cells and mouse photoreceptor-derived 661W cells. In K-1034 cells, GGA (10 microM) induced intracellular Trx, Hsp72, and extracellular Trx but not extracellular Hsp72. Extracellular Trx (0.75 nM) attenuated H2O2 (200 microM)-induced cell damage in 661W cells. Pretreatment with GGA and overexpression of Trx in K-1034 cells counteracted H2O2 (50 microM)-induced attenuation of cellular latex bead incorporation. Protection of phagocytotic activity through induction of Trx and possibly Hsp72 in RPE cells and elimination of oxidative stress in the photoreceptor layer through release of Trx from RPE cells may be mechanisms of GGA-mediated cytoprotection. Therefore, Trx is a neurotrophic factor released from RPE cells and plays a crucial role in maintaining photoreceptor cell integrity.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

Overexpression of thioredoxin prevents thioacetamide-induced hepatic fibrosis in mice.

BACKGROUND/AIMS: Thioredoxin is a small redox-active protein with anti-oxidant and anti-apoptotic effects. We have previously reported that thioacetamide-induced acute hepatitis was attenuated in thioredoxin transgenic mice. The aim of the present study was to investigate the protective effect of thioredoxin for hepatic fibrosis. METHODS: We subjected thioredoxin transgenic mice to thioacetamide-induced hepatic fibrosis. We also studied the effect of thioredoxin on the activation process of primary-cultured hepatic stellate cell. RESULTS: The expression of endogenous thioredoxin was induced in hepatocytes of thioacetamide-induced murine and rat fibrotic livers. Overexpression of thioredoxin inhibited tumor necrosis factor-alpha-induced apoptosis of HepG2 cells. Thioacetamide-induced fibrosis and accumulation of malondialdehyde were suppressed in transgenic mice as compared with wild type mice. Hepatic stellate cells isolated from transgenic mice were less proliferative than those isolated from wild type mice. Recombinant thioredoxin significantly inhibited DNA synthesis of primary-cultured stellate cells under serum or platelet-derived growth factor stimulation. CONCLUSIONS: Thioredoxin has a potential to attenuate hepatic fibrosis via suppressing oxidative stress and inhibiting proliferation of stellate cells.

Animals↗

PubMed2005

Two distinct mechanisms for loss of thioredoxin-binding protein-2 in oxidative stress-induced renal carcinogenesis.

Thioredoxin is a major component of thiol-reducing system. Recently, we identified thioredoxin-binding protein-2 (TBP-2) as a negative regulator of thioredoxin. Here, we report the role of TBP-2 in oxidative renal tubular injury and the subsequent carcinogenesis by ferric nitrilotriacetate. TBP-2 was abundantly expressed in the rat kidney. Immunohistochemical analysis revealed that TBP-2 was present in association with nuclei and mitochondrial intermembrane space in the proximal tubular cells and coimmunoprecipitated with cytochrome c. After acute oxidative tubular damage, TBP-2 protein, but not messenger RNA, markedly decreased, demonstrating shortened half-life of this protein. Most cases of the induced renal cell carcinoma showed undetectable levels of TBP-2 protein, which was associated with the methylation of CpG island in the promoter region. Genome sequence analyses identified the poly-A tract in the 3' untranslated region as a mutation hot spot in this rather nonselective environment. Collectively, the amounts of TBP-2 protein were inversely associated with proliferation of tubular cells, as evaluated by proliferating cell nuclear antigen. These results suggest that loss of TBP-2 is essential for proliferation of not only neoplastic but also non-neoplastic renal tubular cells, and that TBP-2 is a target gene in oxidative stress-induced renal carcinogenesis by ferric nitrilotriacetate.

Animals↗

PubMed2005

Helicobacter felis-induced gastritis was suppressed in mice overexpressing thioredoxin-1.

Thioredoxin-1 (TRX-1) is a redox-active protein involved in scavenging reactive oxygen species and regulating redox-sensitive transcription factors. TRX-1 is induced in various inflammatory conditions and shows cytoprotective action. We investigated the roles of TRX-1 in the host defense mechanism against Helicobacter felis (H. felis) infection. Transgenic (TG) mice overexpressing human TRX-1 and wild-type (WT) mice were orally inoculated with H. felis. After 2 months, histology, oxidative damage, and gene expression of several cytokines, including macrophage inflammatory protein-2 (MIP-2), a murine equivalent to interleukin (IL)-8, in the gastric mucosa were investigated. Furthermore, the effects of TRX-1 on oxidative stress and neutrophil migration were studied both in vivo and in vitro. The gastric mucosa was thickened in H. felis-infected WT mice, but not in infected TRX-1-TG mice. Histologically, all H. felis-infected WT mice developed moderate-to-severe gastritis, whereas the development of gastritis was significantly suppressed in infected TRX-1-TG mice. Oxidative damage markers, 8-hydroxy-2'-deoxyguanosine and malondialdehyde, increased in the stomach of infected WT mice, but not TRX-1-TG mice. Upregulation of IL-1beta and tumor necrosis factor-alpha gene expression in H. felis-infected TRX-1-TG mice was significantly lower than in WT mice. However, upregulation of MIP-2 and IL-7 was not different between the two groups. TRX-1 suppressed oxidative cytotoxicity and DNA damage, and inhibited neutrophil migration both in vivo and in vitro. The present study suggests that overexpression of TRX-1 suppresses H. felis-induced gastritis by inhibiting chemotaxis of neutrophils and reducing oxidative stress.

Animals↗

PubMed2005

Thioredoxin gene expression in rat knee articular cartilage after full-thickness injury.

To study the expression of the antioxidative protein thioredoxin (TRX) in intact and injured articular cartilage, we examined the presence of trx mRNA in rat knee joints by in situ hybridization. Our results showed that in the intact knee, most cells, including articular cartilage chondrocytes, expressed trx mRNA. We examined joints at 1, 7, 14, and 28 days after the infliction of full-thickness cartilage injuries on distal femoral condyles. At 1 day after injury, no significant changes were observed in the wound or in trx expression pattern. However, at 7 to 28 days after injury, the wound became filled with repair tissue. Also, trx expression was detected in differentiating mesenchymal cells in the deeper zones of the wound but not in fibroblast-like cells in the upper part of the repair tissue, toward the joint cavity. This lack of TRX expression in the fibroblast-like cells may underlie the susceptibility of the repair tissue fibrocartilage to oxidative stress.

Animals↗

PubMed2005

Concentrations of thioredoxin, a redox-regulating protein, in umbilical cord blood and breast milk.

Growing evidence indicates that oxidative stress occurs during the fetal-to-neonatal transition. Such stress plays an important role in the pathogenesis of many neonatal diseases. Thioredoxin (TRX), a redox-regulating protein with antioxidant activity, is induced in various cells against oxidative stress and is secreted extracellularly. This study was undertaken to examine the clinical and biological importance of TRX in the perinatal setting. We measured concentrations of TRX in umbilical cord blood and breast milk using a sandwich ELISA. Our study demonstrated that concentrations of TRX in umbilical cord blood were six to seven times higher than those in blood of healthy adults. This study also showed that umbilical concentrations of TRX were correlated significantly with the extent of prematurity of the newborn, and that they were elevated significantly in newborns of mothers with preeclampsia compared to those of mothers without preeclampsia. In contrast, concentrations of coenzyme Q(10) and vitamin E in umbilical blood were lower than adult blood levels. Breast milk concentrations of TRX during the early postpartum period were seven to eight times higher than those in blood of lactating women. Those of the coenzyme Q(10) were lower than adult blood levels, while those of vitamin E were comparable to adult blood levels. Our findings suggest that the systemic release of TRX is enhanced at birth, and that early breast milk is a rich source of this protein. Consequent high levels of TRX in newborns may provide a unique protective mechanism that allows the maintenance of redox balance during the fetal-to-neonatal transition.

Adult↗

PubMed2005

Sulforaphane induces thioredoxin through the antioxidant-responsive element and attenuates retinal light damage in mice.

PURPOSE: Thioredoxin (Trx) is a multifunctional endogenous redox regulator that protects cells against various types of cellular or tissue stresses. This study was conducted to test whether sulforaphane (SF), a naturally occurring isothiocyanate that is highly concentrated in broccoli sprouts, induces Trx in retinal tissues and whether pretreatment with SF protects against light-induced retinal damage in mice. METHODS: Expression of Trx in mouse retina was analyzed by Western blot and immunohistochemistry. Retinal damage was induced by exposure to white light at 6000 lux for 2 hours. To estimate retinal cell damage, the number of cell nuclei and the percentage of TUNEL-positive cells were counted in the outer nuclear layer and the retinal pigment epithelial (RPE) layer and the electroretinograms recorded. To analyze further the mechanism of Trx induction by SF, cultured human K-1034 RPE cells were used. RESULTS: Both intraperitoneal and oral SF induced Trx protein in the neural retina and RPE. The maximum induction of Trx was observed with intraperitoneal SF 0.5 mg/d for 3 days. After exposure to light, mice pretreated with SF had a significantly lower percentage of TUNEL-positive RPE and photoreceptor cells, a significantly higher number of RPE and photoreceptor nuclei, and greater amplitude of ERG a- and b-waves than in the saline-treated mice. In K-1034 cells, 1 microM SF induced Trx protein, whereas 10 microM SF did not damage cells or augment cellular peroxide production, tested by a lactate dehydrogenase (LDH) release assay and 2',7'-dichlorofluorescein diacetate (DCFH-DA)/flow cytometry, respectively. In the luciferase reporter assay, the antioxidant-responsive element (ARE) played a role in SF-induced Trx expression. In the electrophoretic mobility shift assay, SF induced binding of Nrf2, small Maf, and c-Jun to the ARE of the Trx gene. CONCLUSIONS: SF induced Trx in murine retina and effectively reduced retinal light damage. Evidence suggests that the ARE is involved in the mechanism of Trx induction by SF in RPE cells.

Administration, Oral↗

PubMed2005

The involvement of thioredoxin and thioredoxin binding protein-2 on cellular proliferation and aging process.

Recent reports on aging have revealed that many genetic loci affecting life span are closely linked to the machinery either producing or defending oxidative stress. Protective mechanisms against oxidative stress are thus important in countering the aging process. Thioredoxin (TRX) is a small thiol-mediated protein with a redox-active disulfide/dithiol within the conserved active site. TRX transgenic mice are more resistant than control mice to a variety of oxidative stresses including infection and inflammation. Moreover, we observed that the median life span of TRX tg mice was extended up to 135% compared to that of controls. TRX binding protein-2 (TBP-2), which is identical to vitamin D3 upregulated protein 1 (VDUP1), was identified as a binding molecule to TRX, and a negative regulator of TRX function. The expression of TBP-2/VDUP1 is frequently lost in tumor tissue and cell lines, and ectopic expression of TBP-2/VDUP1 suppresses cellular proliferation along with cell cycle arrest at the G1 phase. These findings suggest that TRX and TBP-2/VDUP1 are involved not only in cytoprotective functions against oxidative stress, but also in the regulation of cellular proliferation and the aging process.

Aging↗

PubMed2005

Serum thioredoxin and alpha-tocopherol concentrations in patients with major risk factors.

BACKGROUND: Oxidative stress, which is thought to be increased in subjects with various coronary risk factors, induces thioredoxin (TRX), a redox-active protein. METHODS AND RESULTS: To determine whether oxidative stress is increased, serum concentrations of both TRX and alpha-tocopherol (vitamin E) were determined in 12 control subjects without any coronary risk factors (CONTROL), 6 current smokers (SMOKING), 19 hypertensive patients (HT), 7 hypercholesterolemic patients (HC) and 14 subjects with multiple risk factors (MULTIPLE). Patients with diabetes mellitus were not included. The serum TRX concentrations (mean +/- SD ng/ml) were significantly higher in SMOKING (41+/-10), HT (41+/-17), HC (48+/-15) and MULTIPLE (46+/-15) than in CONTROL (24+/-11). The serum alpha-tocopherol concentrations (mg/g lipids) were not significantly different among CONTROL (4.0+/-0.7), SMOKING (4.0+/-0.8), HT (4.1+/-0.6) and HC (4.2+/-0.6), although the concentration was significantly lower in MULTIPLE (3.3+/-0.7) than in any of the other study groups. CONCLUSIONS: SMOKING, HT, HC and MULTIPLE had significantly higher serum TRX concentrations than CONTROL, suggesting increased oxidative stress. MULTIPLE had a lower serum concentration of antioxidant alpha-tocopherol than any of the other study groups, suggesting impaired or exhausted defense against chronic oxidative stress in the presence of the multiple risk factors.

Adult↗