Thioredoxin in the cardiovascular system

ArticleinJournal of Molecular Medicine 84(12):997-1003 · January 2007with7 Reads
DOI: 10.1007/s00109-006-0109-6 · Source: PubMed
Abstract
The thioredoxin (TRX) system (TRX, TRX reductase, and NADPH) is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status. The impairment of cell redox state alters multiple cell pathways, which may contribute to the pathogenesis of cardiovascular disorders including hypertension, atherosclerosis, and heart failure. In this manuscript, we review the essential roles that TRX plays by limiting oxidative stress directly via antioxidant effects and indirectly by protein-protein interactions with key signaling molecules such as thioredoxin interacting protein (TXNIP). TRX and its endogenous regulators may represent important future targets to develop clinical therapies for diseases associated with oxidative stress.
    • "In addition, data on the importance of Se intake on long-term health are emerging that give rise to other concerns. There are indications that Se is involved in the prevention of diseases such as cancer [3][4][5][6]and cardiovascular diseases [7][8][9]and impaired immune function [10][11], etc. On the other hand, the Se and vitamin E cancer prevention trial (SELECT) reported an increased risk of diabetes mellitus type 2 in humans with a high Se intake (200 μg selenomethionine/day) [12]. "
    [Show abstract] [Hide abstract] ABSTRACT: There is a growing concern for the long-term health effects of selenium (Se) over- or underfeeding. The efficiency of utilization of dietary Se is subject to many factors. Our study in dogs evaluated the effect of diet type (canned versus kibble) and dietary protein concentration on Se digestibility and bioactivity. Canned and kibble diets are commonly used formats of dog food, widely ranging in protein concentration. Twenty-four Labrador retrievers were used and four canned and four kibble diets were selected with crude protein concentrations ranging from 10.1 to 27.5 g/MJ. Crude protein concentration had no influence on the digestibility of Se in either canned or kibble diets, but a lower Se digestibility was observed in canned compared to kibble diets. However, the biological activity of Se, as measured by whole blood glutathione peroxidase, was higher in dogs fed the canned diets than in dogs fed the kibble diets and decreased with increasing crude protein intake. These results indicate that selenium recommendations in dog foods need to take diet type into account.
    Full-text · Article · Apr 2016
    • "Indeed, the transactivation assay in the presence of 4-HNE and the antagonist GSK0660 support the involvement of PPARd in this pro- cess. TXNIP has been linked to atherosclerosis by several in vivo and in vitro studies [50, 69] . Here, we show by immunofluorescence staining of sections from atherosclerotic arteries that both TXNIP and the p21 senescence marker were present in the endothelial cells near the plaque area, supporting the relationship between TXNIP and senescence in vivo. "
    [Show abstract] [Hide abstract] ABSTRACT: Vascular endothelial cell (VEC) senescence is considered an early event in the development of atherosclerotic lesions. Stressful stimuli, in particular oxidative stress, have been linked to premature senescence in the vasculature. Foam cells are a major source of reactive oxygen species and may play a role in the induction of VEC senescence; hence, we investigated their involvement in the induction of VEC senescence in a co-culture transwell system. Primary bovine aortic endothelial cells, exposed to the secretome of THP-1 monocyte-derived foam cells, were analysed for the induction of senescence. Senescence associated β-galactosidase activity and the expression of p16 and p21 were increased, whereas phosphorylated retinoblastoma protein was reduced. This senescent phenotype was mediated by 4-hydroxnonenal (4-HNE), a lipid peroxidation product secreted from foam cells; scavenging of 4-HNE in the co-culture medium blunted this effect. Furthermore, both foam cells and 4-HNE increased the expression of the pro-oxidant thioredoxin-interacting protein (TXNIP). Molecular manipulation of TXNIP expression confirmed its involvement in foam cell-induced senescence. Previous studies showed that peroxisome proliferator-activated receptor (PPAR)δ was activated by 4-hydroalkenals, such as 4-HNE. Pharmacological interventions supported the involvement of the 4-HNE-PPARδ axis in the induction of TXNIP and VEC senescence. The association of TXNIP with VEC senescence was further supported by immunofluorescent staining of human carotid plaques in which the expression of both TXNIP and p21 was augmented in endothelial cells. Collectively, these findings suggest that foam cell-released 4-HNE activates PPARδ in VEC, leading to increased TXNIP expression and consequently to senescence.
    Full-text · Article · Mar 2015
    • "Indeed, the transactivation assay in the presence of 4-HNE and the antagonist GSK0660 support the involvement of PPARd in this pro- cess. TXNIP has been linked to atherosclerosis by several in vivo and in vitro studies [50, 69] . Here, we show by immunofluorescence staining of sections from atherosclerotic arteries that both TXNIP and the p21 senescence marker were present in the endothelial cells near the plaque area, supporting the relationship between TXNIP and senescence in vivo. "
    [Show abstract] [Hide abstract] ABSTRACT: Vascular endothelial cell (VEC) senescence is considered an early event in the development of atherosclerotic lesions. Stressful stimuli, in particular oxidative stress, have been linked to premature senescence in the vasculature. Foam cells are a major source of reactive oxygen species and may play a role in the induction of VEC senescence; hence, we investigated their involvement in the induction of VEC senescence in a co-culture transwell system. Primary bovine aortic endothelial cells, exposed to the secretome of THP-1 monocyte-derived foam cells, were analysed for the induction of senescence. Senescence associated b-galactosidase activity and the expression of p16 and p21 were increased, whereas phosphorylated retinoblastoma protein was reduced. This senescent phenotype was mediated by 4-hydroxnonenal (4-HNE), a lipid per-oxidation product secreted from foam cells; scavenging of 4-HNE in the co-culture medium blunted this effect. Furthermore, both foam cells and 4-HNE increased the expression of the pro-oxidant thioredoxin-interacting protein (TXNIP). Molecular manipulation of TXNIP expression confirmed its involvement in foam cell-induced senescence. Previous studies showed that peroxisome proliferator-activated receptor (PPAR)d was activated by 4-hydroalkenals, such as 4-HNE. Pharmacological interventions supported the involvement of the 4-HNE-PPARd axis in the induction of TXNIP and VEC senescence. The association of TXNIP with VEC senescence was further supported by immunofluorescent staining of human carotid plaques in which the expression of both TXNIP and p21 was augmented in endothelial cells. Collectively, these findings suggest that foam cell-released 4-HNE activates PPARd in VEC, leading to increased TXNIP expression and consequently to senescence. Keywords: atherosclerosis senescence foam cells VEC 4-HNE PPARd TXNIP
    Full-text · Article · Jan 2015
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