Delineating the Role of Glutathione Peroxidase 4 in Protecting Cells Against Lipid Hydroperoxide Damage and in Alzheimer's Disease

Yoo, Min; Gu, Xin-Xing; Xu, Xue Ming; Kim, Jin Young; Carlson, Bradley A.; Patterson, Andrew D.; Cai, Huaibin; Gladyshev, Vadim N.; Hatfield, Dolph L.

doi:10.1089/ars.2009.2891

Cited by 131 publications

(80 citation statements)

References 39 publications

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“…In the present study, aphantoxins induced a significant increase in lipid peroxidation, and this was accompanied by a significant increase in GPx activity. In accordance with our earlier study (Yoo et al, 2010), upregulation GPx is likely to be a resistance mechanism against toxin-induced oxidative stress and lipid peroxidation. Several recent studies have reported GPx upregulation in mouse fibroblasts and neurons following exposure to different chemical toxins (Ran et al, 2006;Yoo et al, 2010), strengthening this interpretation.…”

Section: Cat and Gpx Responsessupporting

confidence: 92%

“…It should be noted that GPx may also reduce organic hydroperoxides to their corresponding alcohols, employing GSH and/or other reducing agents, to protect cells against lipid hydroperoxideinduced damage (Yoo et al, 2010). In the present study, aphantoxins induced a significant increase in lipid peroxidation, and this was accompanied by a significant increase in GPx activity.…”

Section: Cat and Gpx Responsessupporting

confidence: 51%

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Antioxidative responses in zebrafish liver exposed to sublethal doses Aphanizomenon flos-aquae DC-1 aphantoxins

Zhang

Liu

Zhang

et al. 2015

Ecotoxicology and Environmental Safety

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Section: Cat and Gpx Responsessupporting

confidence: 92%

Section: Cat and Gpx Responsessupporting

confidence: 51%

Antioxidative responses in zebrafish liver exposed to sublethal doses Aphanizomenon flos-aquae DC-1 aphantoxins

Zhang

Liu

Zhang

et al. 2015

Ecotoxicology and Environmental Safety

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“…The role played by GPx4 in regulating lipid peroxidestimulated cell death has important physiological implications. Many neurodegenerative diseases are associated with low GSH status leading to inhibition of GPx4 activity (378). Therefore, this novel redox-regulated cell death pathway links GPx4 to preventing neurodegeneration.…”

Section: Selenoprotein Functionmentioning

confidence: 99%

Selenoproteins: Molecular Pathways and Physiological Roles

Labunskyy

Hatfield

Gladyshev³

2014

Physiological Reviews

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1,060

835

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Selenium is an essential micronutrient with important functions in human health and relevance to several pathophysiological conditions. The biological effects of selenium are largely mediated by selenium-containing proteins (selenoproteins) that are present in all three domains of life. Although selenoproteins represent diverse molecular pathways and biological functions, all these proteins contain at least one selenocysteine (Sec), a seleniumcontaining amino acid, and most serve oxidoreductase functions. Sec is cotranslationally inserted into nascent polypeptide chains in response to the UGA codon, whose normal function is to terminate translation. To decode UGA as Sec, organisms evolved the Sec insertion machinery that allows incorporation of this amino acid at specific UGA codons in a process requiring a cis-acting Sec insertion sequence (SECIS) element. Although the basic mechanisms of Sec synthesis and insertion into proteins in both prokaryotes and eukaryotes have been studied in great detail, the identity and functions of many selenoproteins remain largely unknown. In the last decade, there has been significant progress in characterizing selenoproteins and selenoproteomes and understanding their physiological functions. We discuss current knowledge about how these unique proteins perform their functions at the molecular level and highlight new insights into the roles that selenoproteins play in human health.

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“…Oxidative stress reduces the activity of α-secretase and promotes the expression and activation of β-and γ-secretases [100][101][102] . The oxidative stress-induced β-site APP-cleaving enzyme 1, PS1…”

Section: Oxidative Stress Is An Important Contributor To the Pathologmentioning

confidence: 99%

Oxidative stress in Alzheimer’s disease

2014

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Oxidative stress plays a significant role in the pathogenesis of Alzheimer's disease (AD), a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons (lipids, proteins, and nucleic acids) can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, infl ammation, and β-amyloid (Aβ) peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.Keywords: Alzheimer's disease; oxidative stress; β-amyloid; tau; metals; antioxidants ·Review· IntroductionThe human brain, although it constitutes only 2% of the body weight, consumes ~20% of the oxygen supplied by the respiratory system [1] . The high energy-consumption of the brain means that it is more susceptible to oxidative stress than any other organ. As the basic functional unit of the brain, the neuron is particularly vulnerable to oxidative damage because it has a higher metabolic rate than other cells [2] . The oxidation of lipids, proteins, and nucleic acids in neurons is a common pathological feature of Alzheimer's disease (AD) [3] . Neurons contain a large amount of polyunsaturated fatty acids (PUFAs) that can interact with reactive oxygen species (ROS), leading to a selfpropagating cascade of lipid peroxidation and molecular destruction [4] . Furthermore, neurons contain low levels of glutathione, an essential antioxidant for eliminating free radicals [5] . Therefore, neurons are highly susceptible to oxidative stress.An increased oxidative burden has been reported in the brains of non-demented elderly and/or sporadic AD patients [6,7] . Increased levels of oxidative stress biomarkers in the blood reflect such stress in the brain [8,9] . Currently, many blood markers of oxidative stress have been identified in AD patients or related animal models, including protein carbonyls and 3-nitrotyrosine [10,11] , , malondialdehyde (MDA) [12] , 4-hydroxynonenal (4-HNE), and F2-isoprostanes (F2-IsoPs) [13][14][15][16] . Apart from the intracellular accumulation of free radicals, changes in the activities or expressions of antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, have also been described in both the central nervous system and peripheral tissues of AD patients [14,17] . Thus, oxidative stress is an important pathological feature in AD.However, how and where the oxidative stress originates in AD are open questions. Research has suggested that mitochondrial dysfunction [12,18,19] , metal accumulation [12,20,21] , hyperphosphorylated tau [22,23] , inflammation [24,25] , and β-amyloid (Aβ) accumulation [12,19] are the basic mechanisms underlying the induction of oxidative stress. Deficiency or destruction of components of the antioxidant system such as SOD in the mi...

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Delineating the Role of Glutathione Peroxidase 4 in Protecting Cells Against Lipid Hydroperoxide Damage and in Alzheimer's Disease

Cited by 131 publications

References 39 publications

Antioxidative responses in zebrafish liver exposed to sublethal doses Aphanizomenon flos-aquae DC-1 aphantoxins

Antioxidative responses in zebrafish liver exposed to sublethal doses Aphanizomenon flos-aquae DC-1 aphantoxins

Selenoproteins: Molecular Pathways and Physiological Roles

Oxidative stress in Alzheimer’s disease

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