Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus

Greevenbroek, Marleen M.J. van; Vermeulen, Vicky M. M.-J.; Feskens, Edith J. M.; Evelo, Chris T.; Kruijshoop, M.; Hoebee, Barbara; Kallen, Carla; Bruin, T.W.A. de

doi:10.1111/j.1464-5491.2007.02109.x

Cited by 44 publications

(26 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Evidence for a connection between TXNIP and metabolic disease was revealed through a genome wide study that reported high expression of TXNIP in pre‐diabetic and diabetic patient muscle biopsies . Subsequently, specific TXNIP variants have been associated with hyperglycemia and high triglyceride levels in diabetes patients . Correlating with this data, high glucose induces TXNIP expression in numerous cell types associated with metabolic disease (e.g., adipocytes, skeletal myocytes, and β‐cells), and conversely, insulin can repress TXNIP expression .…”

Section: Nlrp3 In Health and Diseasementioning

confidence: 97%

Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation

Yabal

Calleja

Simpson

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Inflammasomes are multimeric protein complexes that induce the cleavage and release of bioactive IL-1 and cause a lytic form of cell death, termed pyroptosis. Due to its diverse triggers, ranging from infectious pathogens and host danger molecules to environmental irritants, the NOD-like receptor protein 3 (NLRP3) inflammasome remains the most widely studied inflammasome to date. Despite intense scrutiny, a universal mechanism for its activation remains elusive, although, recent research has focused on mitochondrial dysfunction or potassium (K + ) efflux as key events. In this review, we give a general overview of NLRP3 inflammasome activation and explore the recently emerging noncanonical and alternative pathways to NLRP3 activation. We highlight the role of the NLRP3 inflammasome in the pathogenesis of metabolic disease that is associated with mitochondrial and oxidative stress. Finally, we interrogate the mechanisms proposed to trigger NLRP3 inflammasome assembly and activation. A greater understanding of how NLRP3 inflammasome activation is triggered may reveal new therapeutic targets for the treatment of inflammatory disease. K E Y W O R D Scaspases, inflammasome, metabolism, mitochondria, reactive oxygen species Abbreviations: AIM2, absent in Melanoma; AMPK, AMP-activated protein kinase; APAF-1, apoptosis protease activating factor-1; ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; BMDCs, bone marrow dendritic

show abstract

Section: Nlrp3 In Health and Diseasementioning

confidence: 97%

Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation

Yabal

Calleja

Simpson

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…Recent studies suggested that Txnip expression is increased in skeletal muscle of human T2DM and impaired glucose tolerance (IGT) patients (59, 60). It was also reported that a genetic variation of the Txnip gene is associated with hypertriglyceridemia and increased diastolic blood pressure (61). Interestingly, Txnip expression is induced by high glucose conditions, while it is reduced by insulin (59).…”

Section: Thioredoxin1/txnip Redoxisome Critical For Pathogenesis Ofmentioning

confidence: 99%

Thioredoxin/Txnip: Redoxisome, as a Redox Switch for the Pathogenesis of Diseases

et al. 2014

View full text Add to dashboard Cite

During the past few decades, it has been widely recognized that Reduction-Oxidation (redox) responses occurring at the intra- and extra-cellular levels are one of most important biological phenomena and dysregulated redox responses are involved in the initiation and progression of multiple diseases. Thioredoxin1 (Trx1) and Thioredoxin2 (Trx2), mainly located in the cytoplasm and mitochondria, respectively, are ubiquitously expressed in variety of cells and control cellular reactive oxygen species by reducing the disulfides into thiol groups. Thioredoxin interacting protein (Txnip/thioredoxin binding protein-2/vitamin D3 upregulated protein) directly binds to Trx1 and Trx2 (Trx) and inhibit the reducing activity of Trx through their disulfide exchange. Recent studies have revealed that Trx1 and Txnip are involved in some critical redox-dependent signal pathways including NLRP-3 inflammasome activation in a redox-dependent manner. Therefore, Trx/Txnip, a redox-sensitive signaling complex is a regulator of cellular redox status and has emerged as a key component in the link between redox regulation and the pathogenesis of diseases. Here, we review the novel functional concept of the redox-related protein complex, named “Redoxisome,” consisting of Trx/Txnip, as a critical regulator for intra- and extra-cellular redox signaling, involved in the pathogenesis of various diseases such as cancer, autoimmune disease, and diabetes.

show abstract

“…TXNIP expression is elevated in the vasculature and the pancreas (Minn et al, 2005) of diabetic animals and in the skeletal muscle of human type 2 diabetes (Parikh et al, 2007). Genetic variation in TXNIP is associated with hypertriglyceridemia and blood pressure in human type 2 diabetes mellitus (van Greevenbroek et al, 2007). …”

Section: Thioredoxin-interacting Protein (Txnip) Is a Metabolic Contrmentioning

confidence: 99%

Thioredoxin-interacting protein and myocardial mitochondrial function in ischemia–reperfusion injury

Yoshioka

Lee

2014

Trends in Cardiovascular Medicine

View full text Add to dashboard Cite

Cellular metabolism and reactive oxygen species (ROS) formation are interrelated processes in mitochondria and are implicated in a variety of human diseases including ischemic heart disease. During ischemia, mitochondrial respiration rates fall. Though seemingly paradoxical, reduced respiration has been observed to be cardioprotective due in part to reduced generation of ROS. Enhanced myocardial glucose uptake is considered beneficial for the myocardium under stress, as glucose is the primary substrate to support anaerobic metabolism. Thus, inhibition of mitochondrial respiration and uncoupling oxidative phosphorylation can protect the myocardium from irreversible ischemic damage. Growing evidence now positions the TXNIP/thioredoxin system at a nodal point linking pathways of antioxidant defense, cell survival, and energy metabolism. This emerging picture reveals TXNIP’s function as a regulator of glucose homeostasis and may prove central to regulation of mitochondrial function during ischemia. In this review, we summarize how TXNIP and its binding partner thioredoxin act as regulators of mitochondrial metabolism. While the precise mechanism remains incompletely defined, the TXNIP-thioredoxin interaction has the potential to affect signaling that regulates mitochondrial bioenergetics and respiratory function with potential cardioprotection against ischemic injury.

show abstract

Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus

Cited by 44 publications

References 31 publications

Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation

Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation

Thioredoxin/Txnip: Redoxisome, as a Redox Switch for the Pathogenesis of Diseases

Thioredoxin-interacting protein and myocardial mitochondrial function in ischemia–reperfusion injury

Contact Info

Product

Resources

About