Peroxiredoxin isoforms are associated with cardiovascular risk factors in type 2 diabetes mellitus

Eter, Eman El; Al-Masri, Abeer A.

doi:10.1590/1414-431x20144142

Cited by 20 publications

(17 citation statements)

References 26 publications

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“…Inflammation often complicates diseases associated with oxidative stress like diabetes mellitus, so this enzyme acts as redox-dependent inflammatory mediator both in vivo and in vitro , modifying the redox status of cell surface receptors and enabling induction of inflammatory responses [26]. So, our findings of significant increased expression in both somatic and embryonic cells support the DOHaD concept and the existence of an interesting crosstalk between PRDX isoform 2 and long-term metabolic diseases and cardiovascular risks [27]. Moreover this antioxidant protection against oxidative stress, also suggest a novel therapeutic mechanism for treating metabolic disorders [71].…”

Section: Discussionsupporting

confidence: 52%

“…In particular the isoform 2, PRDX2, was described upregulated in diabetic patients versus healthy control subjects [27], and this is the reason why we considered this gene of interest. The expression was higher in treated cells of all the four cells lines analysed, with a similar increase of gene expression activity across the range analysed for both somatic (Figures 3I and 3R) and embryonic cells (Figure 4I).…”

Section: Resultsmentioning

confidence: 99%

“…Within this ARE group there are classical antioxidant enzymes such as: superoxide dismutases (SODs), which can directly generate and eliminate the hydrogen peroxide radical [23], catalases (CATs), and glutathione peroxidases (GPXs) [24]. Other important antioxidant enzymes of this system are hemeoxygenase (HMOX) [1], sulfiredoxins (SRXNs) [25], and peroxiredoxins, (PRDXs) [26,27]. The expression of antioxidant enzymes is also regulated by factors like Protein Kinase D1 serine/threonine Kinases (PRDK1), Kelch-Like ECH-Associated Protein 1 (KEAP1) and NFkβ signalling [28–30], being the latter activated by upstream molecules such as mammalian Target of Rapamycin (mTOR) in mammals [31].…”

Section: Introductionmentioning

confidence: 99%

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Differential Response of Human Embryonic Stem and Somatic Cells to Non-Cytotoxic Hydrogen Peroxide Exposure: An Attempt to Model In Vitro the Effects of Oxidative Stress on the Early Embryo

2016

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Human Embryonic Stem Cells (hESCs) potentially offer a unique in vitro model to study how an adverse environment during the early developmental stages post-fertilization can affect the physiology of the undifferentiated embryonic stem cells existing in the early embryo and predispose to long term effects on the offspring, according to the Developmental Origins of Health and Disease (DOHaD) concept. A number of unfavourable conditions can affect the development of the early embryo inducing oxidative stress both in vivo, for instance in gestational diabetes and in vitro, when embryos are derived from Assisted Reproductive Technologies (ART). Therefore, the aim of this study was the development of a novel in vitro model to analyse the effects of oxidative stress and the antioxidant response against Reactive Oxygen Species (ROS) in embryonic stem cells in comparison with somatic cells, fibroblasts and endothelial cells. To this purpose we designed an in vitro protocol based on hydrogen peroxide (H2O2) treatment of 72 h, in order to better resemble the period of embryonic development from the early cleavages to the blastocyst stage. We demonstrate that H2O2 treatment induces the modification of crucial oxidative stress biomarkers like ROS and lipid peroxidation levels, and mobilizes several antioxidant enzymes through NFkβ translocation. Moreover we show differences between somatic and embryonic cells in their antioxidant response towards H2O2 induced damage. Therefore this study presents a promising in vitro model to investigate the effects of oxidative stress conditions on early human embryonic cells.

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Section: Discussionsupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential Response of Human Embryonic Stem and Somatic Cells to Non-Cytotoxic Hydrogen Peroxide Exposure: An Attempt to Model In Vitro the Effects of Oxidative Stress on the Early Embryo

2016

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“…Indeed, decreased mRNA levels of Prdx1 and Ucp-1 , two important players of the antioxidant defense, were detected in isolated rats with respect to animals reared in group. Prdx1 is a member of the peroxiredoxin family of antioxidant enzymes, reducing hydrogen peroxide and alkyl hydroperoxides ( He et al, 2015 ), involved in the maintenance of different physiological functions, as well as in the pathogenesis of several diseases, such as inflammation-mediated disorders, tumorigenesis ( El Eter and Al-Masri, 2015 ) and neurological illnesses ( Zhu et al, 2012 ). Interestingly, a decrease in Prdx1 has been also associated with the development of impaired metabolism-associated disorders, such as type 2 diabetes and cardiovascular diseases ( El Eter and Al-Masri, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Visceral Fat Dysfunctions in the Rat Social Isolation Model of Psychosis

et al. 2017

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Medication with neuroleptics has been associated with adipose tissue dysfunctions and, in particular, with increased visceral fat amount. However, several studies suggested that antipsychotic treatment might not be the main responsible of fat mass accumulation, as this has been also described in not treated psychotic patients. One of the most used “drug-free” rodent models of psychosis is the social isolation rearing of young adult rats, which provides a non-pharmacologic method of inducing long-term alterations reminiscent of symptoms seen in psychotic patients. Recent data highlighted a crucial role of redox imbalance in adipose tissue dysfunctions, in terms of decreased antioxidant defense and increased reactive oxygen species (ROS). Here, we investigated possible oxidative stress-related biomolecular alterations associated with visceral fat increase in 7 week isolated rats. To this purpose, we quantified total and visceral fat amount by using dual-energy X-ray (DEXA) absorptiometry. On visceral fat, we analyzed the expression of specific ROS-producer genes (Nox1, Nox4, Hmox-1), antioxidant enzymes (Prdx1 and Ucp-1) and oxidative stress-induced damage markers (Cidea, Slc2a4, and Acacb). The impact of oxidative stress on beta3-adrenergic receptors (Adrb3), at both mRNA and protein level, was also assessed. We found that 7 weeks of social isolation induced an increase in total and visceral fat, associated with a decrease in Prdx1 (mRNA and protein) as well as Ucp-1 mRNA levels and an enhanced expression of Nox1 (mRNA and protein) and Hmox-1 mRNA. No differences were detected in Nox4 mRNA levels between grouped and isolated animals. Elevations in Cidea, Slc2a4, and Acacb expression in visceral fat of isolated animals accounted for oxidative stress-related damage in this tissue, further associated with a significant increase in Adrb3 mRNA and protein. Our results provide a novel understanding of the pathological link existing among psychosocial stress-induced psychosis, adipose tissue dysfunctions and redox imbalance, opening new therapeutic perspectives for the treatment of alterations in peripheral tissues associated with this mental disorder.

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“…have diminished capacity to handle oxidative stress. It is intriguing that serum of patients with T2D has higher levels of circulating PRDX4 than controls (34) although the cell source of the PRDX4 is not yet known (11; 35).…”

Section: Discussionmentioning

confidence: 99%

A reference map of the human proinsulin biosynthetic interaction network

Tran

Pottekat

Mir

et al. 2019

Preprint

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The beta-cell secretory protein synthetic machinery is dedicated to insulin production, and recent reports suggest that both proinsulin misfolding and accompanying beta-cell oxidative stress could be common features in type 2 diabetes (T2D). Despite the critical role of insulin in organismal homeostasis, the precise network of interactions from early proinsulin synthesis and folding in the ER, to its subsequent trafficking through the secretory pathway, remain poorly defined. In the present study we utilized a human proinsulin-specific monoclonal antibody for affinity purification mass spectrometry, to yield unbiased profiling of the proinsulin interactome in human islets. The data reveal that human proinsulin interacts with a network of ER folding factors (including chaperones: e.g. ERDJ5, ERDJ3, GRP94, and BiP; and oxidoreductases: e.g. QSOX1, DUOX2, and PRDX4) that are remarkably conserved across both genders and 3 ethnicities. Knockdown of one of the most prominent hits, peroxiredoxin-4 (PRDX4) in MIN6 beta-cells, rendered proinsulin more susceptible to misfolding. Additionally, oxidant exposure in human islets enhanced proinsulin:BiP interactions with augmented proinsulin misfolding. Finally, oxidant exposure in human islets also led to sulfonylation of PRDX4, a modification known to inactivate peroxiredoxins. Interestingly, we observed significantly higher levels of sulfonylated (inactive) PRDX4 in islets from patients with T2D compared to that of normal islets. Taken together, these data provide a detailed reference map of the human proinsulin interaction network and suggest critical unrecognized areas for study in insulin biosynthesis, beta cell function, and T2D.

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Peroxiredoxin isoforms are associated with cardiovascular risk factors in type 2 diabetes mellitus

Cited by 20 publications

References 26 publications

Differential Response of Human Embryonic Stem and Somatic Cells to Non-Cytotoxic Hydrogen Peroxide Exposure: An Attempt to Model In Vitro the Effects of Oxidative Stress on the Early Embryo

Differential Response of Human Embryonic Stem and Somatic Cells to Non-Cytotoxic Hydrogen Peroxide Exposure: An Attempt to Model In Vitro the Effects of Oxidative Stress on the Early Embryo

Visceral Fat Dysfunctions in the Rat Social Isolation Model of Psychosis

A reference map of the human proinsulin biosynthetic interaction network

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