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Junji Yodoi - One of the best experts on this subject based on the ideXlab platform.
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Human Thioredoxin-1 attenuates the rate of lipopolysaccharide-induced preterm delivery in mice in association with its anti-inflammatory effect
Pediatric research, 2016Co-Authors: Fumihiko Namba, Junji Yodoi, Mikiko Kobayashi-miura, Taro Goda, Yukiko Nakura, Fumiko Nishiumi, Aoi Son, Akio Kubota, Itaru YanagiharaAbstract:Human Thioredoxin-1 attenuates the rate of lipopolysaccharide-induced preterm delivery in mice in association with its anti-inflammatory effect
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Thioredoxin-1 Protects against Neutrophilic Inflammation and Emphysema Progression in a Mouse Model of Chronic Obstructive Pulmonary Disease Exacerbation
PloS one, 2013Co-Authors: Naoya Tanabe, Yuma Hoshino, Satoshi Marumo, Hirofumi Kiyokawa, Susumu Sato, Daisuke Kinose, Kazuko Uno, Shigeo Muro, Toyohiro Hirai, Junji YodoiAbstract:Background Exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression. However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established. Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS)-induced emphysema. We aimed to determine whether Thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms. Results Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C)], an agonist for virus-induced innate immunity. Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice. Exposure to CS and poly(I:C) challenge accelerated emphysema progression in C57Bl/6 mice. Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression. Poly(I:C) caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF) release in the lung exposed to CS. Late neutrophilic inflammation was caused by persistent GM-CSF release, which Thioredoxin-1 ameliorated. Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1), and the suppressive effects of Thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1. Conclusion Using a mouse model of COPD exacerbation, we demonstrated that Thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression. Our findings deepen understanding of the mechanisms underlying the regulation of neutrophilic inflammation by Thioredoxin-1 and indicate that Thioredoxin-1 could have potential as a drug to counteract COPD exacerbation.
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Thioredoxin-1 Attenuates Early Graft Loss after Intraportal Islet Transplantation in Mice
PloS one, 2013Co-Authors: Kengo Asami, Junji Yodoi, Akiko Inagaki, Takehiro Imura, Satoshi Sekiguchi, Keisei Fujimori, Hiroshi Masutani, Susumu Satomi, Noriaki Ohuchi, Masafumi GotoAbstract:Aims Recent studies suggest that decreasing oxidative stress is crucial to achieve successful islet transplantation. Thioredoxin-1 (TRX), which is a multifunctional redox-active protein, has been reported to suppress oxidative stress. Furthermore, it also has anti-inflammatory and anti-apoptotic effects. In this study, we investigated the effects of TRX on early graft loss after islet transplantation.
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Induction of endoplasmic reticulum stress and the modulation of Thioredoxin-1 in formaldehyde-induced neurotoxicity
Neurotoxicology, 2012Co-Authors: Fu-cheng Luo, Sheng-dong Wang, Hajime Nakamura, Junji Yodoi, Jia Zhou, Jie BaiAbstract:Formaldehyde (FA), a common environmental pollutant, has toxic effects on central nervous system. The detailed mechanisms on FA-induced neurotoxicity have not been fully elucidated. In this study, we found that glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) expression, biomarkers of endoplasmic reticulum (ER) stress, were increased and pro-caspase-12 was decreased after PC12 cells exposure to FA. These results suggest that FA actually induces ER stress. Thioredoxin-1 (Trx-1) has various biological activities, including the control of redox balance, the modulation of ER stress and inhibition of apoptosis. In the present study, Trx-1 expression was increased at early stage, but decreased at late stage after FA treatment. Knockdown of Trx-1 expression increased the susceptibility of PC12 cells to FA-induced neurotoxicity. We also found that ginsenoside Rg1 had the potential to induce Trx-1 expression and attenuated neurotoxicity induced by FA. ER stress caused by FA was suppressed by ginsenoside Rg1. These data indicate that Trx-1 is a therapeutic candidate for protecting against FA-induced neurotoxicity.
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The expression of Thioredoxin-1 in preterm delivery placenta.
Redox report : communications in free radical research, 2012Co-Authors: Jun-ying Song, Xudong Dong, Yan Chen, Guixian Chen, Hong Liang, Hajime Nakamura, Junji Yodoi, Jie BaiAbstract:Preterm delivery (PTD) is the leading cause of infant mortality and morbidity. However, the mechanism at the molecular level is still unknown. Placental inflammatory response and oxidative stress are associated with PTD. Thioredoxin-1 (TRX-1) regulates oxidative stress, inflammation, and the activities of transcription factors. Objectives The objective was to detect in placental tissues the expressions of TRX-1 and the TRX-1-related molecules: tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), Thioredoxin-1-binding protein-2 (TBP-2), hypoxia inducible transcription factor 1α (HIF-1α), and forkhead box protein O3A (FoxO3A). Methods PTD was defined as gestation of
Jie Bai - One of the best experts on this subject based on the ideXlab platform.
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The role of Thioredoxin-1 in resisting methamphetamine-induced rewarding effect.
Behavioural brain research, 2017Co-Authors: Mengbing Huang, Xiaoshuang Zhou, Lihua Yang, Kong Lingpin, Jie BaiAbstract:Methamphetamine (METH) is a highly addictive drug of abuse which induces behavioral sensitization and rewarding effects. Thioredoxin-1 (Trx-1) is a redox protein and plays roles in regulating activity of transcription factor, such as cAMP responsive element-binding protein (CREB), AP-1, p53, is emerging as an important modulator of neuronal function. It has been reported that Trx-1 is involved in morphine dependence. In this study, we examined the rewarding effect after METH administration by conditioned place preference (CPP) of mice, and detected the levels of dopamine and the activity of cAMP responsive element-binding protein (CREB), the expressions of ΔFosB and cyclin-dependent kinase 5 (CDK5) in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in mice. Our results showed that the expression of METH-CPP was occluded in Trx-1 overexpression transgenic (TG) mice. The increase of dopamine level induced by METH was not further higher in Trx-1 TG mice. METH decreased the expression of Trx-1 which was restored in TG mice. The activity of CREB and the expressions of ΔFosB and CDK5 were increased by METH in wile-type mice, which were not further increased in TG mice. These results suggest that overexpression of Trx-1 may occlude the CPP induced by METH through regulating the activity of CREB and the expression of ΔFosB.
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Increased Expression of Thioredoxin-1 Binding Protein-2 in Placentas in Preeclampsia.
The Journal of reproductive medicine, 2017Co-Authors: Xudong Dong, Yue-mei Feng, Yanxue Cai, Jiang Jiang, Jie BaiAbstract:OBJECTIVE: To examine the expressions of Thioredoxin-1 (TRX-1) and Thioredoxin-1 binding protein-2 (TBP-2) in placentas affected by preeclampsia. STUDY DESIGN: We examined the mRNA levels of TRX-1, TBP-2, cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) in preeclamptic (n=20) and normal placentas (n=18) by quantitative reverse transcriptase-polymerase chain reaction. RESULTS: We found the mRNA level of TRX-1 was significantly decreased (p
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The Role of Thioredoxin-1 in Suppression Sepsis Through Inhibiting Mitochondrial-Induced Apoptosis in Spleen.
Shock (Augusta Ga.), 2017Co-Authors: Guobing Chen, Xiaoshuang Zhou, Mengbing Huang, Xiaoqin Mao, Jie BaiAbstract:ABSTRACTSepsis is a serious public health issue and the leading cause of death in critically ill patients in intensive care units. Thioredoxin-1 (Trx-1) is a protein of regulating redox, as well as a modulator of inflammation and apoptosis. Our previous study reported that Trx-1 decreased endoplasmi
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The overexpression of Thioredoxin-1 suppressing inflammation induced by methamphetamine in spleen.
Drug and alcohol dependence, 2015Co-Authors: Kong Lingpin, Jin-jing Jia, Xiaoshuang Zhou, Jiao-long Fang, Jie BaiAbstract:Abstract Background Methamphetamine (METH) is an addictive psychostimulant and has been shown to induce oxidative stress and inflammation in various tissues. Thioredoxin-1 (Trx-1) plays the roles in regulating redox and inhibiting inflammation. Whether Trx-1 is involved in METH-induced inflammation is still unknown. Methods The present study was designed to investigate inflammatory factors in spleen of wild type and Trx-1 overexpression transgenic mice after METH treatment. Results We found the mRNA level of Trx-1 was decreased and mRNA level of Trx-1 binding protein-2 (TBP-2) was increased. The mRNA levels of tumor necrosis factor-α (TNF-α), interferon-γ(IFN-γ), interleukin-2 (IL-2), T-bet and signal transducer and activators of transcription 4 (STAT 4) were increased and the mRNA levels of IL-10, GA-TA-binding protein-3 (GATA-3) and STAT 6 were decreased. Overexpression of Trx-1 reversed the above effects induced by METH. Conclusion The present study showed for the first time that Trx-1 overexpression suppressed the inflammation induced by METH.
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Thioredoxin-1 was required for CREB activity by methamphetamine in rat pheochromocytoma cells.
Cellular and molecular neurobiology, 2012Co-Authors: Sheng-dong Wang, Jie BaiAbstract:Methamphetamine (METH) is one of the most commonly abused agents by illicit-drug users. Thioredoxin-1 (Trx-1) plays important biological roles both in intra- and extracellular compartments, including in regulation of various intracellular molecules via thiol redox control. In this study, we found that Trx-1 was induced by METH in rat pheochromocytoma PC12 cells. Furthermore, PI3K/Akt pathway was involved in METH-induced increase of Trx-1 expression. An increase in phosphorylated cAMP response element-binding protein (CREB) was also observed after exposure of PC12 cells to METH, which was inhibited by a PI3K inhibitor, LY294002. In addition, the siRNA targeted toTrx-1 reduced the level of phosphorylated CREB by METH, suggesting Trx-1 is necessary for increased activity of CREB by METH. The results obtained in this study showed that Trx-1 might play a role in the actions of METH.
Hajime Nakamura - One of the best experts on this subject based on the ideXlab platform.
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Induction of endoplasmic reticulum stress and the modulation of Thioredoxin-1 in formaldehyde-induced neurotoxicity
Neurotoxicology, 2012Co-Authors: Fu-cheng Luo, Sheng-dong Wang, Hajime Nakamura, Junji Yodoi, Jia Zhou, Jie BaiAbstract:Formaldehyde (FA), a common environmental pollutant, has toxic effects on central nervous system. The detailed mechanisms on FA-induced neurotoxicity have not been fully elucidated. In this study, we found that glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) expression, biomarkers of endoplasmic reticulum (ER) stress, were increased and pro-caspase-12 was decreased after PC12 cells exposure to FA. These results suggest that FA actually induces ER stress. Thioredoxin-1 (Trx-1) has various biological activities, including the control of redox balance, the modulation of ER stress and inhibition of apoptosis. In the present study, Trx-1 expression was increased at early stage, but decreased at late stage after FA treatment. Knockdown of Trx-1 expression increased the susceptibility of PC12 cells to FA-induced neurotoxicity. We also found that ginsenoside Rg1 had the potential to induce Trx-1 expression and attenuated neurotoxicity induced by FA. ER stress caused by FA was suppressed by ginsenoside Rg1. These data indicate that Trx-1 is a therapeutic candidate for protecting against FA-induced neurotoxicity.
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The expression of Thioredoxin-1 in preterm delivery placenta.
Redox report : communications in free radical research, 2012Co-Authors: Jun-ying Song, Xudong Dong, Yan Chen, Guixian Chen, Hong Liang, Hajime Nakamura, Junji Yodoi, Jie BaiAbstract:Preterm delivery (PTD) is the leading cause of infant mortality and morbidity. However, the mechanism at the molecular level is still unknown. Placental inflammatory response and oxidative stress are associated with PTD. Thioredoxin-1 (TRX-1) regulates oxidative stress, inflammation, and the activities of transcription factors. Objectives The objective was to detect in placental tissues the expressions of TRX-1 and the TRX-1-related molecules: tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), Thioredoxin-1-binding protein-2 (TBP-2), hypoxia inducible transcription factor 1α (HIF-1α), and forkhead box protein O3A (FoxO3A). Methods PTD was defined as gestation of
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anti oxidative anti cancer and anti inflammatory actions by Thioredoxin 1 and Thioredoxin binding protein 2
Pharmacology & Therapeutics, 2010Co-Authors: Rie Watanabe, Hajime Nakamura, Hiroshi Masutani, Junji YodoiAbstract:Thioredoxin 1 (Trx 1) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys- that is ubiquitously present in the human body. Trx 1 is a defensive protein induced by various stresses and has anti-oxidative, anti-apoptotic and anti-inflammatory effects. The anti-oxidative effect of Trx 1 is mediated by the dithiol-disulfide exchange in the active site. Trx 1 is able to interact with certain molecules, one of which is Thioredoxin-binding protein-2 (TBP-2)/Vitamin D3 upregulated protein 1 (VDUP1)/Thioredoxin interacting protein (TXNIP). TBP-2 was originally identified as a negative regulator of Trx 1 and acts as a cell growth suppressor and a regulator in lipid/glucose metabolism. Trx 1 and TBP-2 play crucial roles in pathophysiological mechanisms in metabolic disorders, cancer and inflammation. Here we discuss pharmacological aspects of Trx 1 and TBP-2 in these diseases and propose potential therapeutic approaches for intractable oxidative stress-related disorders.
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Panaxatriol saponins extracted from Panax notoginseng induces Thioredoxin-1 and prevents 1-methyl-4-phenylpyridinium ion-induced neurotoxicity.
Journal of ethnopharmacology, 2009Co-Authors: Fu-cheng Luo, Sheng-dong Wang, Hajime Nakamura, Junji Yodoi, Jie BaiAbstract:Abstract Aim of the study Thioredoxin-1 has various biologic activities, including the control of redox balance and the inhibition of apoptosis. The current study was designed to examine the effects of panaxatriol saponins (PTS) extracted from Panax notoginseng on Thioredoxin-1 expression and 1-methyl-4-phenylpyridinium ion-induced injury. Materials and methods Using PC12 cells and Kunming mice, we test Thioredoxin-1 expression after PTS treatment by Western blot. The protective effect of PTS against 1-methyl-4-phenylpyridinium ion-induced injury was assessed by MTT assay and LDH release assay. Results PTS induced Thioredoxin-1 expression in vitro and in vivo, and attenuated 1-methyl-4-phenylpyridinium ion-induced cell death of PC12 cells. Conclusions PTS is a new inducer of Thioredoxin-1 and has a possible potential as a therapeutic agent for neurodegenerative diseases including Parkinson's disease.
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Thioredoxin 1 delivery as new therapeutics.
Advanced drug delivery reviews, 2009Co-Authors: Hajime Nakamura, Yuma Hoshino, Hiroaki Okuyama, Yoshiyuki Matsuo, Junji YodoiAbstract:Thioredoxin 1 (Trx 1) is a redox-active small protein ubiquitously present in human body. It is one of the defensive proteins induced in response to various stress conditions. In addition to its anti-oxidative effect by dithiol-disulfide exchange in its active site, Trx 1 has anti-apoptotic and anti-inflammatory effects. Trx 1 overexpression has been shown to be effective in a wide variety of animal models for oxidative and inflammatory disorders. An administration of recombinant Trx 1 protein is also effective in animal models especially for severe acute lung diseases where Trx 1 is likely to act with its anti-inflammatory properties. Trx 1 in circulation shows anti-chemotactic effects for neutrophils and inhibitory effects against macrophage migration inhibitory factor (MIF). Neovascularization is also suppressed by Trx 1 via inhibition of the complement activation. Here we discuss precise mechanisms of Trx 1 and potential therapeutic approach of this molecule.
Nilanjana Maulik - One of the best experts on this subject based on the ideXlab platform.
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Thioredoxin-1 augments wound healing and promote angiogenesis in a murine ischemic full-thickness wound model
Surgery, 2018Co-Authors: Ibnalwalid Saad, Craig T. Fournier, Rickesha L. Wilson, Rajesh Lakshmanan, Vaithinathan Selvaraju, Mahesh Thirunavukkarasu, J. Alexander Palesty, David W. Mcfadden, Nilanjana MaulikAbstract:Abstract Background Nonhealing wounds are a continuing health problem in the United States. Overproduction of reactive oxygen species is a major causative factor behind delayed wound healing. Previously we reported that Thioredoxin-1 treatment could alleviate oxidative stress under ischemic conditions, such as myocardial infarction and hindlimb ischemia. In this study, we explored the potential for Thioredoxin-1 gene therapy to effectively aid wound healing through improved angiogenesis in a murine ischemic wound model. Methods Full-thickness, cutaneous, ischemic wounds were created in the dorsum skin flap of 8- to 12-week-old CD1 mice. Nonischemic wounds created lateral to the ischemic skin flap served as internal controls. Mice with both ischemic wounds and nonischemic wounds were treated with Adeno-LacZ (1 × 109 pfu) or Adeno-Thioredoxin-1 (1 × 109 pfu), injected intradermally around the wound. Digital imaging was performed on days 0, 3, 6, and 9 to assess the rate of wound closure. Tissue samples collected at predetermined time intervals were processed for immunohistochemical analysis. Results No significant differences in wound closure were identified among the nonischemic wounds control, nonischemic wounds-LacZ, and nonischemic wounds–Thioredoxin-1 groups. Hence, only mice with ischemic wounds were further analyzed. The ischemic wounds–Thioredoxin-1 group had significant improvement in wound closure on days 6 and 9 after surgery compared with the ischemic wounds control and ischemic wounds-LacZ groups. Immunohistochemical analysis indicated increased Thioredoxin-1, vascular endothelial cell growth factor, and β-catenin levels in the ischemic wounds–Thioredoxin-1 group compared with the ischemic wounds control and ischemic wounds-LacZ groups, as well as increased capillary density and cell proliferation, as represented by Ki-67 staining. Conclusion Taken together, Thioredoxin-1 gene therapy promotes vascular endothelial cell growth factor signaling and re-epithelialization and activates wound closure in mice with ischemic wounds.
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Thioredoxin 1 Enhances Neovascularization and Reduces Ventricular Remodeling During Chronic Myocardial Infarction: A Study Using Thioredoxin 1 Transgenic Mice
Journal of molecular and cellular cardiology, 2010Co-Authors: Ram Sudheer Adluri, Mahesh Thirunavukkarasu, Samson Mathews Samuel, Lijun Zhan, Gautam Maulik, Yuzo Akita, Hajime Otani, Nilanjana MaulikAbstract:Abstract Oxidative stress plays a crucial role in disruption of neovascularization by alterations in Thioredoxin 1 (Trx1) expression and its interaction with other proteins after myocardial infarction (MI). We previously showed that Trx1 has angiogenic properties, but the possible therapeutic significance of overexpressing Trx1 in chronic MI has not been elucidated. Therefore, we explored the angiogenic and cardioprotective potential of Trx1 in an in vivo MI model using transgenic mice overexpressing Trx1. Wild-type (W) and Trx1 transgenic (Trx1Tg/+) mice were randomized into W sham (WS), Trx1Tg/+ sham (TS), WMI, and TMI. MI was induced by permanent occlusion of LAD coronary artery. Hearts from mice overexpressing Trx1 exhibited reduced fibrosis and oxidative stress and attenuated cardiomyocyte apoptosis along with increased vessel formation compared to WMI. We found significant inhibition of Trx1 regulating proteins, TXNIP and AKAP 12, and increased p-Akt, p-eNOS, p-GSK-3β, HIF-1α, β-catenin, VEGF, Bcl-2, and survivin expression in TMI compared to WMI. Echocardiography performed 30 days after MI revealed significant improvement in myocardial functions in TMI compared to WMI. Our study identifies a potential role for Trx1 overexpression and its association with its regulatory proteins TXNIP, AKAP12, and subsequent activation of Akt/GSK-3β/β-catenin/HIF-1α-mediated VEGF and eNOS expression in inducing angiogenesis and reduced ventricular remodeling. Hence, Trx1 and other proteins identified in our study may prove to be potential therapeutic targets in the treatment of ischemic heart disease.
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Thioredoxin-1 Gene Therapy Enhances Angiogenic Signaling and Reduces Ventricular Remodeling in Infarcted Myocardium of Diabetic Rats
Circulation, 2010Co-Authors: Samson Mathews Samuel, Mahesh Thirunavukkarasu, Suresh Varma Penumathsa, Srikanth Koneru, Lijun Zhan, Gautam Maulik, Perumana R. Sudhakaran, Nilanjana MaulikAbstract:Background— The present study evaluated the reversal of diabetes-mediated impairment of angiogenesis in a myocardial infarction model of type 1 diabetic rats by intramyocardial administration of an adenoviral vector encoding Thioredoxin-1 (Ad.Trx1). Various studies have linked diabetes-mediated impairment of angiogenesis to dysfunctional antioxidant systems in which Thioredoxin-1 plays a central role. Methods and Results— Ad.Trx1 was administered intramyocardially in nondiabetic and diabetic rats immediately after myocardial infarction. Ad.LacZ was similarly administered to the respective control groups. The hearts were excised for molecular and immunohistochemical analysis at predetermined time points. Myocardial function was measured by echocardiography 30 days after the intervention. The Ad.Trx1-administered group exhibited reduced fibrosis, oxidative stress, and cardiomyocyte and endothelial cell apoptosis compared with the diabetic myocardial infarction group, along with increased capillary and arter...
Shinichi Oka - One of the best experts on this subject based on the ideXlab platform.
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Abstract 877: Thioredoxin-1 Maintains Cardiac Function and Metabolic Gene Expression via mTOR Signaling
Circulation Research, 2019Co-Authors: Shinichi Oka, Wataru Mizushima, Chun-yang Huan, Junichi SadoshimaAbstract:Thioredoxin-1 (Trx1) is a 12 kDa oxidoreductase that reduces proteins with disulfide bonds through thiol disulfide exchange reactions. Several lines of evidence show that Trx1 protects cardiomyocyt...
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Abstract 17498: Cardiac-Specific Thioredoxin-1 Knockout Induces Cardiac Dysfunction
Circulation, 2017Co-Authors: Shinichi Oka, Narayani Nagarajan, Wataru Mizushima, Kevin Schesing, Jaemin Byun, Shohei Ikeda, Junichi SadoshimaAbstract:Thioredoxin-1 (Trx1) is a 12 KDa oxidoreductase, which reduces proteins with disulfide bonds through thiol-disulfide exchange reactions. Several lines of evidences show that Trx1 protects cardiomyocytes against stress, such as ischemia and pressure overload. However, due to the embryonic lethality of systemic Trx1 knockout mice, the role of endogenous Trx1 in cardiac function had not been tested with a loss-of-function model. In this study, we generated cardiac-specific Trx1 knockout (Trx1cKO) mice with Trx1floxflox and αMHC-Cre transgenic mice to elucidate the physiological role of Trx1. The protein levels of Trx1 were significantly reduced in Trx1cKO mice in a cardiac-specific manner. The Trx1cKO mice were viable but started dying at 2 weeks of age. The median survival age was 3.6 weeks. None of the mice survived for longer than 8 weeks. Histochemical analyses showed a trend of increased cardiomyocyte cell size in Trx1cKO mice (relative cell size: Wild-type (WT): 1; Trx1cKO: 1.8), whereas apoptotic cell...
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Abstract 16734: Thioredoxin-1 Potentiates Mtor Activity Through Direct Reduction In Cardiomyocytes
Circulation, 2016Co-Authors: Shinichi Oka, Tsuyoshi Hirata, Hiroaki Yaginuma, Dan Shao, Narayani Nagarajan, Junichi SadoshimaAbstract:Thioredoxin 1 (Trx1) is a 12 KDa oxidoreductase, which reduces proteins with disulfide bonds through thiol-disulfide exchange reactions. Trx1 protects cardiomyocytes (CMs) against stress, such as i...
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Thioredoxin 1-Mediated Post-Translational Modifications: Reduction, Transnitrosylation, Denitrosylation, and Related Proteomics Methodologies
Antioxidants & redox signaling, 2011Co-Authors: Andrew M. Parrott, Tong Liu, Stefano M. Marino, Vadim N. Gladyshev, Mohit Jain, Ahmet Tarik Baykal, Shinichi OkaAbstract:Abstract Despite the significance of redox post-translational modifications (PTMs) in regulating diverse signal transduction pathways, the enzymatic systems that catalyze reversible and specific oxidative or reductive modifications have yet to be firmly established. Thioredoxin 1 (Trx1) is a conserved antioxidant protein that is well known for its disulfide reductase activity. Interestingly, Trx1 is also able to transnitrosylate or denitrosylate (defined as processes to transfer or remove a nitric oxide entity to/from substrates) specific proteins. An intricate redox regulatory mechanism has recently been uncovered that accounts for the ability of Trx1 to catalyze these different redox PTMs. In this review, we will summarize the available evidence in support of Trx1 as a specific disulfide reductase, and denitrosylation and transnitrosylation agent, as well as the biological significance of the diverse array of Trx1-regulated pathways and processes under different physiological contexts. The dramatic prog...
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Overexpression of Thioredoxin-1 in transgenic mice attenuates adriamycin-induced cardiotoxicity.
Circulation, 2002Co-Authors: Keisuke Shioji, Hajime Nakamura, Shinichi Oka, Hiroshi Masutani, Chiharu Kishimoto, Zuyi Yuan, Junji YodoiAbstract: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 c...