Homocysteine alters Redox Regulation through Thioredoxin‐Interacting Protein: A Novel role of Forkhead Transcription Factor (FOXO‐3a/FKHR‐L1)

Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. Recent studies indicate an evolving role of TXNIP in the pathogenesis of complex diseases such as metabolic disorders, neurological disorders, and inflammatory illnesses. In addition, TXNIP has gained significant attention due to its wide range of functions in energy metabolism, insulin sensitivity, improved insulin secretion, and also in the regulation of glucose and tumor suppressor activities in various cancers. This review aims to highlight the roles of TXNIP in the field of diabetology, neurodegenerative diseases, and inflammation. TXNIP is found to be a promising novel therapeutic target in the current review, not only in the aforementioned diseases but also in prolonged microvascular and macrovascular diseases. Therefore, TXNIP inhibitors hold promise for preventing the growing incidence of complications in relevant diseases.

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Thioredoxin-interacting protein, a potential pharmacological target for the treatment of depression

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2018.10.357 ◽

2018 ◽

Vol 128 ◽

pp. S135

Author(s):

Hong Zhou ◽

Hua Tan ◽

Veni Bharti ◽

Eftekhar Eftekharpour ◽

Jun-Feng Wang

Keyword(s):

Protein A ◽

Interacting Protein ◽

Thioredoxin Interacting Protein ◽

Treatment Of Depression ◽

Pharmacological Target

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Mitochondrial Localization of the Yeast Forkhead Factor Hcm1

International Journal of Molecular Sciences ◽

10.3390/ijms21249574 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9574

Author(s):

María José Rodríguez Colman ◽

Joaquim Ros ◽

Elisa Cabiscol

Keyword(s):

Transcription Factor ◽

Transcriptional Activity ◽

Spindle Pole ◽

Respiratory Metabolism ◽

Mitochondrial Localization ◽

Transcription Factor Family ◽

Forkhead Transcription Factor ◽

Mitochondrial Transcription Factor ◽

Gradient Density

Hcm1 is a member of the forkhead transcription factor family involved in segregation, spindle pole dynamics, and budding in Saccharomyces cerevisiae. Our group described the role of Hcm1 in mitochondrial biogenesis and stress resistance, and in the cellular adaptation to mitochondrial respiratory metabolism when nutrients decrease. Regulation of Hcm1 activity occurs at the protein level, subcellular localization, and transcriptional activity. Here we report that the amount of protein increased in the G1/S transition phase when the factor accumulated in the nucleus. In the G2/M phases, the Hcm1 amount decreased, and it was translocated outside the nucleus with a network-like localization. Preparation of highly purified mitochondria by a sucrose gradient density demonstrated that Hcm1 colocalized with mitochondrial markers, inducing expression of COX1, a mitochondrial encoded subunit of cytochrome oxidase, in the G2/M phases. Taken together, these results show a new localization of Hcm1 and suggest that it acts as a mitochondrial transcription factor regulating the metabolism of this organelle.

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Endothelial pro-atherosclerotic response to extracellular diabetic-like environment: Possible role of thioredoxin-interacting protein

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfp768 ◽

2010 ◽

Vol 25 (7) ◽

pp. 2141-2149 ◽

Cited By ~ 17

Author(s):

T. Zitman-Gal ◽

J. Green ◽

M. Pasmanik-Chor ◽

V. Oron-Karni ◽

J. Bernheim

Keyword(s):

Interacting Protein ◽

Thioredoxin Interacting Protein

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The Role of the Forkhead Transcription Factor, FOXM1, in Pituitary Gland Development

10.1210/endo-meetings.2011.part2.p2.p1-384 ◽

2011 ◽

pp. P1-384-P1-384

Author(s):

Adam Gerrit Ploegman ◽

Buffy S Ellsworth

Keyword(s):

Transcription Factor ◽

Pituitary Gland ◽

Forkhead Transcription Factor ◽

Gland Development

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Long non-coding RNA MEG3 silencing and microRNA-214 restoration elevate osteoprotegerin expression to ameliorate osteoporosis by limiting TXNIP

10.21203/rs.2.19130/v1 ◽

2019 ◽

Author(s):

Rui Ding ◽

ZhengTao Gu ◽

ChangSheng Yang ◽

CaiQiang Huang ◽

QingChu Li ◽

...

Keyword(s):

Interacting Protein ◽

Blood Samples ◽

Rat Models ◽

Thioredoxin Interacting Protein ◽

Non Coding Rna ◽

Proliferation And Differentiation ◽

Non Coding Rnas ◽

Long Non Coding Rna ◽

Rat Osteoblasts

Abstract BackgroundLong non-coding RNAs (LncRNAs) have been found to regulate innumerable diseases, yet the role of lncRNA MEG3 in osteoporosis (OP) has rarely been discussed. Here, we intend to probe into the mechanism of MEG3 on OP development by modulating microRNA-214 (miR-214) and thioredoxin-interacting protein (TXNIP)MethodsRat models of OP were established. MEG3, miR-214, and TXNIP mRNA expression in rat femoral tissues was detected, along with TXNIP, PCNA, cyclin D1, OCN, RUNX2, Osteolix, OPG, and PANKL protein expression. Ca, P and ALP contents in rat blood samples were also determined. Primary osteoblasts were isolated and cultured. Viability, COL-I, COL-II and COL-Χ contents, ALP content and activity, and mineralized nodule area of rat osteoblasts in each group were further detected.ResultsMEG3 and TXNIP were overexpressed while miR-214 was underexpressed in femoral tissues of OP rats. MEG3 silencing and miR-214 overexpression increased BMD, BV/TV, Tb.N, Tb.Th, the number of osteoblasts, collagen area and OPG expression, and downregulated PANKL of femoral tissues in OP rats. MEG3 silencing and miR-214 overexpression elevated Ca and P contents and reduced ALP content in OP rats’ blood, elevated viability, differentiation ability, COL-I and COL-Χ contents and ALP activity, and abated COL-II content of osteoblasts. MEG3 specifically bound to miR-214 to regulate TXNIP.ConclusionCollectively, we demonstrated that MEG3 silencing and miR-214 overexpression promote proliferation and differentiation of osteoblasts in OP by downregulating TXNIP, which further improves OP.

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The role of the forkhead transcription factor, Foxc1, in the development of the mouse lacrimal gland

Developmental Dynamics ◽

10.1002/dvdy.20702 ◽

2006 ◽

Vol 235 (4) ◽

pp. 1074-1080 ◽

Cited By ~ 14

Author(s):

Deidre Mattiske ◽

Paula Sommer ◽

Susan H. Kidson ◽

Brigid L.M. Hogan

Keyword(s):

Transcription Factor ◽

Lacrimal Gland ◽

Forkhead Transcription Factor

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Hypertrophic cardiomyopathy in high-fat diet-induced obesity: role of suppression of forkhead transcription factor and atrophy gene transcription

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00319.2008 ◽

2008 ◽

Vol 295 (3) ◽

pp. H1206-H1215 ◽

Cited By ~ 72

Author(s):

Cindy X. Fang ◽

Feng Dong ◽

D. Paul Thomas ◽

Heng Ma ◽

Leilei He ◽

...

Keyword(s):

Transcription Factor ◽

Palmitic Acid ◽

High Fat Diet ◽

Weight Control ◽

Dominant Negative ◽

High Fat ◽

Forkhead Transcription Factor ◽

Diet Induced Obesity ◽

Intracellular Ca

Cellular hypertrophy is regulated by coordinated pro- and antigrowth machineries. Foxo transcription factors initiate an atrophy-related gene program to counter hypertrophic growth. This study was designed to evaluate the role of Akt, the forkhead transcription factor Foxo3a, and atrophy genes muscle-specific RING finger (MuRF)-1 and atrogin-1 in cardiac hypertrophy and contractile dysfunction associated with high-fat diet-induced obesity. Mice were fed a low- or high-fat diet for 6 mo along with a food-restricted high-fat weight control group. Echocardiography revealed decreased fractional shortening and increased end-systolic diameter and cardiac hypertrophy in high-fat obese but not in weight control mice. Cardiomyocytes from high-fat obese but not from weight control mice displayed contractile and intracellular Ca2+ defects including depressed maximal velocity of shortening/relengthening, prolonged duration of shortening/relengthening, and reduced intracellular Ca2+ rise and clearance. Caspase activities were greater in high-fat obese but not in weight control mouse hearts. Western blot analysis revealed enhanced basal Akt and Foxo3a phosphorylation and reduced insulin-stimulated phosphorylation of Akt and Foxo3a without changes in total protein expression of Akt and Foxo3a in high-fat obese hearts. RT-PCR and immunoblotting results displayed reduced levels of the atrogens atrogin-1 and MuRF-1, the upregulated hypertrophic markers GATA4 and ciliary neurotrophic factor receptor-α, as well as the unchanged calcineurin and proteasome ubiquitin in high-fat obese mouse hearts. Transfection of H9C2 myoblast cells with dominant-negative Foxo3a adenovirus mimicked palmitic acid (0.8 mM for 24 h)-induced GATA4 upregulation without an additive effect. Dominant-negative Foxo3a-induced upregulation of pAkt and repression of phosphatase and tensin homologue were abrogated by palmitic acid. These results suggest a cardiac hypertrophic response in high-fat diet-associated obesity at least in part through inactivation of Foxo3a by the Akt pathway.

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