scholarly journals Induction of thioredoxin-interacting protein is mediated by oxidative stress, calcium, and glucose after brain injury in mice

2012 ◽  
Vol 46 (2) ◽  
pp. 440-449 ◽  
Author(s):  
Gab Seok Kim ◽  
Joo Eun Jung ◽  
Purnima Narasimhan ◽  
Hiroyuki Sakata ◽  
Pak H. Chan
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

Abstract 6253: Increased Expression of Thioredoxin Interacting Protein Promotes Oxidative Stress and Contributes to the Pathogenesis Of Diabetic Cardiomyopathy

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kim A Connelly ◽  
Darren J Kelly ◽  
Michael Zhang ◽  
Kerri Thai ◽  
Andrew Advani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
High Glucose ◽  
Diastolic Heart Failure ◽  
Transgenic Rat ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Neonatal Cardiomyocytes

Background: Alterations in the thioredoxin (TRX) antioxidant system have been implicated in the pathogenesis of cardiac injury, particularly in the diabetic setting. While constitutively present, TRX activity is reduced by the presence of its endogenous inhibitor, thioredoxin interacting protein (TxnIP). We hypothesized that by increasing TxnIP, diabetes may reduce TRX activity and contribute to oxidative stress. Methods: Cell culture studies were performed using the H9C2 rat cardiomyoblast cell line and neonatal cardiomyocytes isolated from 1 day old Sprague Dawley rat neonates. In-vivo studies were performed using a hemodynamically-validated rodent model of diabetic diastolic heart failure, the diabetic (mRen-2)27 transgenic rat (Ren-2). Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was used as a measure of oxidative stress. Results: In- vitro, high glucose (25mmol/l) resulted in increased TxnIP mRNA expression in both neonatal cardiomyocytes as well as H92C cells (2.21 ± 0.6 v 1.00 ± 0.19, p<0.05 compared to normoglycaemic conditions) with a 45% reduction in TRX activity (0.11 ± 0.01 v 0.061± 0.003, p<0.01). In-vivo, diabetes led to a 250% rise in TxnIP mRNA expression compared to control (2.54 ± 0.5 v 1.00 ± 0.11, p<0.001) that was accompanied by a three fold rise in urinary 8-OHdG (680 ± 280 v 1395 ± 391 ng/ml, p<0.001). Conclusion: In both the in vitro and in vivo settings, high glucose leads to TxnIP over-expression associated with reduced TRX activity thereby increasing oxidative stress and implicating this system in the pathogenesis of the cardiac dysfunction that characterizes the diabetic state. Pharmacological manipulation of the TRX-TxnIP system may represent a novel target to reduce diabetic complications.

Thioredoxin-interacting protein links oxidative stress to inflammasome activation

2009 ◽  
Vol 11 (2) ◽  
pp. 136-140 ◽  
Author(s):  
Rongbin Zhou ◽  
Aubry Tardivel ◽  
Bernard Thorens ◽  
Inpyo Choi ◽  
Jürg Tschopp
Keyword(s):  
Oxidative Stress ◽  
Inflammasome Activation ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

Diabetes impairs exercise training-associated thioredoxin response and glutathione status in rat brain

2009 ◽  
Vol 106 (2) ◽  
pp. 461-467 ◽  
Author(s):  
Zekine Lappalainen ◽  
Jani Lappalainen ◽  
Niku K. J. Oksala ◽  
David E. Laaksonen ◽  
Savita Khanna ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Exercise Training ◽  
Redox Status ◽  
Antioxidant Defenses ◽  
Sod Activity ◽  
Interacting Protein ◽  
Glutathione Peroxidase 1 ◽  
Thioredoxin Interacting Protein ◽  
Streptozotocin Induced Diabetes ◽  
Diabetic Brain

Regular exercise plays an important preventive and therapeutic role in oxidative stress-associated diseases such as diabetes and its complications. Thiol antioxidants including thioredoxin (TRX) and glutathione (GSH) have a crucial role in controlling cellular redox status. In this study, the effects of 8 wk of exercise training on brain TRX and GSH systems, and antioxidant enzymes were tested in rats with or without streptozotocin-induced diabetes. We found that in untrained animals, the levels of TRX-1 (TRX1) protein and activity, and thioredoxin-interacting protein (TXNip) were similar in diabetic and nondiabetic animals. Exercise training, however, increased TRX1 protein in nondiabetic animals without affecting TXNip levels, whereas diabetes inhibited the effect of training on TRX1 protein and also increased TXNip mRNA. In addition, the proportion of oxidized glutathione (GSSG) to total GSH was increased in animals with diabetes, indicating altered redox status and possibly increased oxidative stress. Glutathione peroxidase-1 (GPX1) levels were not affected by diabetes or exercise training, although diabetes increased total GPX activity. Both diabetes and exercise training decreased glutathione reductase (GRD) activity and cytosolic superoxide dismutase (Cu,Zn-SOD) levels. Nevertheless, diabetes or training had no effect on Cu,Zn-SOD mRNA, Mn-SOD protein, total SOD activity, or catalase mRNA, protein, or activity. Our findings suggest that exercise training increases TRX1 levels in brain without a concomitant rise in TXNip, and that experimental diabetes is associated with an incomplete TRX response to training. Increased oxidative stress may be both a cause and a consequence of perturbed antioxidant defenses in the diabetic brain.

scholarly journals The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target

2021 ◽  
Vol 22 (4) ◽  
pp. 1693
Author(s):  
Alison Domingues ◽  
Julia Jolibois ◽  
Perrine Marquet de Rougé ◽  
Valérie Nivet-Antoine
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Therapeutic Target ◽  
Redox Status ◽  
Interacting Protein ◽  
Cellular Redox ◽  
Thioredoxin Interacting Protein ◽  
Potential Biomarker ◽  
Ischemic Diseases

Thioredoxin interacting protein (TXNIP) is a metabolism- oxidative- and inflammation-related marker induced in cardiovascular diseases and is believed to represent a possible link between metabolism and cellular redox status. TXNIP is a potential biomarker in cardiovascular and ischemic diseases but also a novel identified target for preventive and curative medicine. The goal of this review is to focus on the novelties concerning TXNIP. After an overview in TXNIP involvement in oxidative stress, inflammation and metabolism, the remainder of this review presents the clues used to define TXNIP as a new marker at the genetic, blood, or ischemic site level in the context of cardiovascular and ischemic diseases.

scholarly journals Nitrosative/Oxidative Stress Conditions Regulate Thioredoxin-Interacting Protein (TXNIP) Expression and Thioredoxin-1 (TRX-1) Nuclear Localization

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e84588 ◽  
Author(s):  
Fernando Toshio Ogata ◽  
Wagner Luiz Batista ◽  
Adriano Sartori ◽  
Tarsis Ferreira Gesteira ◽  
Hiroshi Masutani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nuclear Localization ◽  
Stress Conditions ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Thioredoxin 1

scholarly journals Neuroprotective Activity of Coptisine fromCoptis chinensis(Franch)

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Thomas Friedemann ◽  
Udo Schumacher ◽  
Yi Tao ◽  
Alexander Kai-Man Leung ◽  
Sven Schröder
Keyword(s):  
Oxidative Stress ◽  
Neuroprotective Effect ◽  
Neuroprotective Activity ◽  
Important Ingredient ◽  
Promising Candidate ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Chinese Herbal ◽  
Tert Butylhydroperoxide ◽  
Study Results

Coptis chinensisrhizomes (CR) are one important ingredient of traditional Chinese herbal formulas such as San-Huang-Xie-Xin-Tang which is used for treatment of cardiovascular and neurodegenerative diseases. Recent studies suggest that the extract of CR might be a potential therapeutic agent for amelioration of neurological disorders associated with oxidative stress. In the present study we aimed at revealing the main active compound(s) of the CR extract and at investigating the mechanism of action. Four main alkaloids of the CR extract (berberine, coptisine, jatrorrhizine, and palmatine) were selected for this study. Results showed that out of those alkaloids only pretreatment with coptisine significantly attenuated tert-butylhydroperoxide induced reduction of cell viability, increased rate of apoptosis, and declined mitochondrial membrane potential. Elisa assay and quantitative real-time PCR analyses revealed that thioredoxin-interacting protein (TXNIP) gene expression was downregulated by coptisine, which could explain the neuroprotective effect, hypothetically, by strengthening the thioredoxin defense system against oxidative stress and attenuation of apoptosis signal-regulating kinase (Ask1) mediated apoptotic signaling. A comparison between coptisine and CR extract identified coptisine as the main single component responsible for the neuroprotective effect. Based on the results the CR extract and coptisine are promising candidate agents for prevention or improvement of diabetic neuropathy and neurodegenerative disorders.

scholarly journals Hyperglycemia Promotes Oxidative Stress through Inhibition of Thioredoxin Function by Thioredoxin-interacting Protein

2004 ◽  
Vol 279 (29) ◽  
pp. 30369-30374 ◽  
Author(s):  
P. Christian Schulze ◽  
Jun Yoshioka ◽  
Tomosaburo Takahashi ◽  
Zhiheng He ◽  
George L. King ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

scholarly journals Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases

2020 ◽  
Vol 21 (24) ◽  
pp. 9357
Author(s):  
Haruka Tsubaki ◽  
Ikuo Tooyama ◽  
Douglas Gordon Walker
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Stress Factors ◽  
Brain Diseases ◽  
Neural Cells ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Pyrin Domain ◽  
Glucose And Lipid Metabolism

The development of new therapeutic approaches to diseases relies on the identification of key molecular targets involved in amplifying disease processes. One such molecule is thioredoxin-interacting protein (TXNIP), also designated thioredoxin-binding protein-2 (TBP-2), a member of the α-arrestin family of proteins and a central regulator of glucose and lipid metabolism, involved in diabetes-associated vascular endothelial dysfunction and inflammation. TXNIP sequesters reduced thioredoxin (TRX), inhibiting its function, resulting in increased oxidative stress. Many different cellular stress factors regulate TXNIP expression, including high glucose, endoplasmic reticulum stress, free radicals, hypoxia, nitric oxide, insulin, and adenosine-containing molecules. TXNIP is also directly involved in inflammatory activation through its interaction with the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome complex. Neurodegenerative diseases such as Alzheimer’s disease have significant pathologies associated with increased oxidative stress, inflammation, and vascular dysfunctions. In addition, as dysfunctions in glucose and cellular metabolism have been associated with such brain diseases, a role for TXNIP in neurodegeneration has actively been investigated. In this review, we will focus on the current state of the understanding of possible normal and pathological functions of TXNIP in the central nervous system from studies of in vitro neural cells and the brains of humans and experimental animals with reference to other studies. As TXNIP can be expressed by neurons, microglia, astrocytes, and endothelial cells, a complex pattern of regulation and function in the brain is suggested. We will examine data suggesting TXNIP as a therapeutic target for neurodegenerative diseases where further research is needed.

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