Selenoprotein P: Properties, Functions, and Regulation

Mostert, Volker

doi:10.1006/abbi.2000.1735

Cited by 112 publications

(91 citation statements)

References 57 publications

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“…This protein family performs a wide spectrum of biological functions, ranging from antioxidant protection and thyroid hormone metabolism to proper reproductive performance (22). Moreover, selenoproteins are crucial to many cellular functions as demonstrated by the fact that the overexpression of glutathione peroxidase 1 (29,30) and thioredoxin reductase (31) has been found to inhibit apoptosis as well as the finding that selenoprotein P seems to be a survival factor for neurons (32,33).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

Hwang¹,

Sin²,

Kim³

et al. 2008

Int J Mol Med

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Abstract. Selenoprotein is associated with a variety of serious diseases, including infectious diseases, neurodegenerative disorders, cancer and cardiovascular disease. The aim of this study was to produce a new transgenic (Tg) rat expressing human selenoprotein M (SelM) in order to examine the protective function of the antioxidant status in vivo. To achieve this, a new lineage of Tg rats was produced by the microinjection of pCMV/GFP-hSelM constructs into a fertilized rat egg. Several conclusions can be drawn based on the results of the present study. The human SelM gene was successfully expressed at both the transcription and protein levels in the CMV/GFP-hSelM Tg rats. This Tg rat showed a different enzyme activity for the antioxidant protein in the various tissues examined. In response to the 2,2'-azobiz(2-amidinopropane) dihydrochloride (AAPH) injection, the Tg rats showed a lower level of antioxidant and H 2 O 2 concentration as the activity of the antioxidant enzyme was maintained at a higher level in the Tg rats than in the non-Tg rats. Also, the neutrophil-to-lymphocyte ratio was significantly increased in this Tg rat, even though the level of corticosterone remained unchanged in both genotypes. Thus, the results of this study demonstrated that the CMV/GFP-hSelM Tg rat can serve as an animal model for the maintenance of a high level of antioxidant status and can be used to study the biological function of selenoprotein in infectious diseases, cardiovascular disease and cancer.

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Section: Discussionmentioning

confidence: 99%

Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

Hwang¹,

Sin²,

Kim³

et al. 2008

Int J Mol Med

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show abstract

“…[199][200][201][202] Sel P has heparin-binding properties, carries approximately 60% of plasma selenium, is expressed in the liver, and has up to 10 selenocysteine residues in the full-length form. 200,203,204 Plasma levels are approximately 5-6 mg/L.…”

Section: Selenoprotein P (Sel P)mentioning

confidence: 99%

Redox Regulation in the Extracellular Environment

Ottaviano

Handy

Loscalzo

2008

Circ J

128

100

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Molecular oxygen is involved in the oxidation of substrates used to produce energy; however, normal metabolism can also generate harmful (bio)chemical byproducts. These deleterious products are partially reduced forms of oxygen, and include free radicals such as superoxide anion radical, hydroxyl radical, or highly oxidizing non-radical species such as hydrogen peroxide (H2O2) and lipid peroxides, which are collectively known as ROS. 1 ROS typically derive from normal metabolism, activated leukocytes, and ambient oxygen in the environment. The production and accumulation of ROS and their downstream effects can be controlled or attenuated by antioxidants. When the ability of antioxidants to eliminate harmful cellular and extracellular ROS is compromised, the balance between ROS generation and antioxidant function to eliminate ROS is shifted in favor of an accumulation of oxidants, which defines the state of oxidative stress in a cell or organism. Oxidative damage can affect DNA, lipids, and proteins, and eventually compromise cell integrity. Many studies have implicated ROS in the pathological processes leading to heart disease, cancer, aging, AIDS, and inflammatory and autoimmune diseases.Oxidants, especially free radicals, are highly reactive. Superoxide can react within milliseconds with nitric oxide (NO) to produce peroxynitrite (ONOO -), a reactive nitrogen species (RNS). The nitrosium cation and nitroxyl anion are other RNS derived from NO. 2 Peroxynitrite is a strong oxidant involved in the nitrosative modification of proteins and lipids. Owing to its rapid reaction with NO, superoxide may modulate NO bioavailability and, subsequently, regulate vascular function. 3 Circulation Journal Vol.72, January 2008The cytosol, mitochondria, peroxisomes, and plasma are all potential sites of ROS formation. 4 The major sources of ROS are enzymatic via nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), xanthine oxidase, myeloperoxidase, endothelial NO synthase (eNOS), or as a consequence of normal mitochondrial respiration. In vascular cells, other enzymatic sources of ROS include cytochrome P450 isoenzymes, lipoxygenase, cyclooxygenase, heme oxygenase, and glucose oxidase. 1,3,[5][6][7] Most reviews to date have focused on the role of intracellular antioxidants that eliminate ROS from the intracellular environment. There are, however, several extracellular antioxidants that also play an equally important role in limiting ROS accumulation in the extracellular environment. Along with limiting ROS accumulation, extracellular redox status is essential for maintaining protein stability and function.The major enzymes important for the elimination of extracellular H2O2 are glutathione peroxidase-3 (GPx-3) and peroxiredoxin IV (Prx IV). Other extracellular antioxidants involved in ROS elimination include paraoxonase (PON), thioredoxin (Trx), Trx reductase (TrxR), glutaredoxin (Grx), extracellular superoxide dismutase (EC-SOD), and extracellular glutathione (GSH).Some of these antioxidants, notably glutathione...

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“…Of particular note is a 43-fold increase in mRNA from CCMs for an allele of the DQW1-β gene from major histocompatibility complex Class II HLA-DR2-DW12, also reflecting an apparently unique immune response in CCMs. In addition, a fourfold increase in mRNA was noted in CCMs of a gene coding for selenoprotein P, a plasma protein associated with vascular endothelium and a prime target for peroxynitrite toxicity (29).…”

Section: Differential Gene Discovery In Avms and Ccmsmentioning

confidence: 99%

Differential Gene Expression in Human Cerebrovascular Malformations

et al. 2003

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OBJECTIVE-We sought to identify genes with differential expression in cerebral cavernous malformations (CCMs), arteriovenous malformations (AVMs), and control superficial temporal arteries (STAs) and to confirm differential expression of genes previously implicated in the pathobiology of these lesions. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript METHODS-Total ribonucleic acid was isolated from four CCM, four AVM, and three STA surgical specimens and used to quantify lesion-specific messenger ribonucleic acid expression levels on human gene arrays. Data were analyzed with the use of two separate methodologies: gene discovery and confirmation analysis. RESULTS-The gene discovery method identified 42 genes that were significantly up-regulated and 36 genes that were significantly down-regulated in CCMs as compared with AVMs and STAs (P = 0.006). Similarly, 48 genes were significantly up-regulated and 59 genes were significantly down-regulated in AVMs as compared with CCMs and STAs (P = 0.006). The confirmation analysis showed significant differential expression (P < 0.05) in 11 of 15 genes (angiogenesis factors, receptors, and structural proteins) that previously had been reported to be expressed differentially in CCMs and AVMs in immunohistochemical analysis. CONCLUSION-We identify numerous genes that are differentially expressed in CCMs andAVMs and correlate expression with the immunohistochemistry of genes implicated in cerebrovascular malformations. In future efforts, we will aim to confirm candidate genes specifically related to the pathobiology of cerebrovascular malformations and determine their biological systems and mechanistic relevance. KeywordsArteriovenous malformations; Cavernous malformations; Gene arrays; Gene expression Cerebrovascular malformations (CVMs) are lesions with an abnormal vessel phenotype that predisposes patients to hemorrhagic strokes, seizures, focal neurological deficits, and other clinical manifestations (4,22). They include arteriovenous malformations (AVMs) and cerebral cavernous malformations (CCMs) and have distinct clinicopathological radiological profiles (14,30). The AVMs are tangled complexes of tortuous vessels representing fistulous connections between arteries and veins, and they lack an intervening capillary bed. They reveal preserved features of mature vessel wall phenotype altered by high flow and hemodynamic stress, including arterial, nidal, and venous aneurysms (5,6,28). The CCMs are characterized by caverns filled with blood or thrombus and are lined with a single layer of endothelial cells. These low-flow lesions are associated with brittle vasculature and repetitive oozing (5,6). The CCMs lack inter-endothelial cell tight junctions and mature vessel wall angio-architecture (8, 37).Little is known about the mechanisms of genesis or the progression of these lesions. Several proteins are abnormally expressed in AVMs and CCMs. Our group and others have demonstrated by performing immunohistochemical analysis that vascular endoth...

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Selenoprotein P: Properties, Functions, and Regulation

Cited by 112 publications

References 57 publications

Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

Redox Regulation in the Extracellular Environment

Differential Gene Expression in Human Cerebrovascular Malformations

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