Redox Pioneer: Professor Vadim N. Gladyshev

Hatfield, Dolph L.

doi:10.1089/ars.2015.6625

Cited by 4 publications

(4 citation statements)

References 68 publications

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“…The SEPP polymorphism rs7579 is located in a region corresponding to the 3′-UTR, 26 where a UGA codon is read as a selenocysteine (Sec) codon during selenoprotein synthesis. 48 This SNP may alter the efficiency of Sec incorporation into SePP. 49 The rs3877899 polymorphism is located in the coding region of the SEPP gene and may regulate the stability of SePP protein and cellular Se uptake.…”

Section: Discussionmentioning

confidence: 99%

Pro198Leu polymorphism affects the selenium status and GPx activity in response to Brazil nut intake

et al. 2016

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Selenoproteins play important roles in antioxidant mechanisms, and are thus hypothesised to have some involvement in the pathology of certain types of dementia. Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are both thought to involve impaired biological activity of certain selenoproteins. Previously, supplementation with a selenium-rich Brazil nut (Bertholletia excelsa) has shown potential in reducing cognitive decline in MCI patients, and could prove to be a safe and effective nutritional approach early in the disease process to slow decline. Here, we have conducted a pilot study that examined the effects of a range of single nucleotide polymorphisms (SNPs) in genes encoding the selenoproteins glutathione peroxidase (GPX1) and selenoprotein P (SEPP) in response to selenium supplementation via dietary Brazil nuts, including selenium status, oxidative stress parameters and GPX1 and SEPP gene expression. Our data suggest that GPX1 Pro198Leu rs1050450 genotypes may differentially affect the selenium status and GPx activity. Moreover, rs7579 and rs3877899 SNPs in SEPP gene, as well as GPX1 rs1050450 genotypes can influence the expression of GPX1 and SEPP mRNA in response to Brazil nuts intake. This small study gives cause for larger investigations into the role of these SNPs in both the selenium status and response to selenium dietary intake, especially in chronic degenerative conditions like MCI and AD.

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Section: Discussionmentioning

confidence: 99%

Pro198Leu polymorphism affects the selenium status and GPx activity in response to Brazil nut intake

et al. 2016

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“…Cytosolic isoform Trx 1 is also protective, promoting endothelial angiogenic activities, and interacting with ASK-1 to inhibit pro-apoptotic pathways [42]. Trx 1 overexpression is protective in mouse myocardial infarction [43] and ex vivo ischemia-reperfusion [44]. Thioredoxin-interacting protein (TXNIP) has been considered as an endogenous Trx inhibitor which is increased in diabetes.…”

Section: Animal Models Of Ischemic Neovascularizationmentioning

confidence: 99%

Redox regulation of ischemic limb neovascularization – What we have learned from animal studies

2017

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Mouse hindlimb ischemia has been widely used as a model to study peripheral artery disease. Genetic modulation of the enzymatic source of oxidants or components of the antioxidant system reveal that physiological levels of oxidants are essential to promote the process of arteriogenesis and angiogenesis after femoral artery occlusion, although mice with diabetes or atherosclerosis may have higher deleterious levels of oxidants. Therefore, fine control of oxidants is required to stimulate vascularization in the limb muscle. Oxidants transduce cellular signaling through oxidative modifications of redox sensitive cysteine thiols. Of particular importance, the reversible modification with abundant glutathione, called S-glutathionylation (or GSH adducts), is relatively stable and alters protein function including signaling, transcription, and cytoskeletal arrangement. Glutaredoxin-1 (Glrx) is an enzyme which catalyzes reversal of GSH adducts, and does not scavenge oxidants itself. Glrx may control redox signaling under fluctuation of oxidants levels. In ischemic muscle increased GSH adducts through Glrx deletion improves in vivo limb revascularization, indicating endogenous Glrx has anti-angiogenic roles. In accordance, Glrx overexpression attenuates VEGF signaling in vitro and ischemic vascularization in vivo. There are several Glrx targets including HIF-1α which may contribute to inhibition of vascularization by reducing GSH adducts. These animal studies provide a caution that excess antioxidants may be counter-productive for treatment of ischemic limbs, and highlights Glrx as a potential therapeutic target to improve ischemic limb vascularization.

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“…Damage to proteins can lead to loss of their stability and function (25–27) and to impaired protein synthesis (24) and degradation (28). While protein damage is only one of a broad set of changes impacting the proteome with age (15, 29), it is an important component. We focus not on the genetics and biochemistry of any particular gene or protein, but on the cell-wide biophysics of how proteins fold (30), the impact of temperature and oxidation (25, 31), and how proteostasis declines with age.…”

mentioning

confidence: 99%

Proteostasis collapse is a driver of cell aging and death

Santra

Dill

Graff

2019

Proc. Natl. Acad. Sci. U.S.A.

140

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What molecular processes drive cell aging and death? Here, we model how proteostasis—i.e., the folding, chaperoning, and maintenance of protein function—collapses with age from slowed translation and cumulative oxidative damage. Irreparably damaged proteins accumulate with age, increasingly distracting the chaperones from folding the healthy proteins the cell needs. The tipping point to death occurs when replenishing good proteins no longer keeps up with depletion from misfolding, aggregation, and damage. The model agrees with experiments in the worm Caenorhabditis elegans that show the following: Life span shortens nonlinearly with increased temperature or added oxidant concentration, and life span increases in mutants having more chaperones or proteasomes. It predicts observed increases in cellular oxidative damage with age and provides a mechanism for the Gompertz-like rise in mortality observed in humans and other organisms. Overall, the model shows how the instability of proteins sets the rate at which damage accumulates with age and upends a cell’s normal proteostasis balance.

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Redox Pioneer: Professor Vadim N. Gladyshev

Cited by 4 publications

References 68 publications

Pro198Leu polymorphism affects the selenium status and GPx activity in response to Brazil nut intake

Pro198Leu polymorphism affects the selenium status and GPx activity in response to Brazil nut intake

Redox regulation of ischemic limb neovascularization – What we have learned from animal studies

Proteostasis collapse is a driver of cell aging and death

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