Selenoprotein R is a zinc-containing stereo-specific methionine sulfoxide reductase

Kryukov, Gregory V.; Kumar, Rakesh; Koç, Ahmet; Sun, Zhonghua; Gladyshev, Vadim N.

doi:10.1073/pnas.072603099

Cited by 246 publications

(233 citation statements)

References 40 publications

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“…Such was the glutaredoxin-encoding GRX1 gene that was reported to respond primarily to HP (Grant et al, 2000). In addition, YCL033C, which encodes a methionine (R)-sulfoxide reductase, and is coexpressed with GRX1, was previously reported to protect cells from oxidative protein damage, specifically that caused by HP (Kryukov et al, 2002). Together with GRX3 and GRX5, these genes define a small HP-specific regulon.…”

Section: Discussionmentioning

confidence: 99%

Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress

Shapira

Segal

Botstein

2004

MBoC

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The effects of oxidative stress on yeast cell cycle depend on the stress-exerting agent. We studied the effects of two oxidative stress agents, hydrogen peroxide (HP) and the superoxide-generating agent menadione (MD). We found that two small coexpressed groups of genes regulated by the Mcm1-Fkh2-Ndd1 transcription regulatory complex are sufficient to account for the difference in the effects of HP and MD on the progress of the cell cycle, namely, G1 arrest with MD and an S phase delay followed by a G2/M arrest with HP. Support for this hypothesis is provided by fkh1fkh2 double mutants, which are affected by MD as we find HP affects wild-type cells. The apparent involvement of a forkhead protein in HP-induced cell cycle arrest, similar to that reported for Caenorhabditis elegans and human, describes a potentially novel stress response pathway in yeast. INTRODUCTIONReactive oxygen species (ROS) are by-products of aerobic metabolism, but are also attributes of the extracellular environment. They pose a threat to organisms by damaging a variety of cellular macromolecules, including DNA, membrane lipids, and proteins and are implicated with carcinogenesis, aging, and numerous degenerative diseases (Finkel and Holbrook, 2000;Neumann et al., 2003). The major ROS derived from oxygen are superoxide ions, hydrogen peroxide (HP), and hydroxy radicals, ordered here by increasing reactivity (reviewed in Shackelford et al., 2000).Oxidative stress in yeast has been studied by exposing cells to agents that are already reactive, typically HP, or drugs that cause the intracellular accumulation of reactive oxygen species (Godon et al., 1998;Dumond et al., 2000;Gasch et al., 2000). Menadione (MD) is such a drug, generating reactive superoxide ions, which can be further oxidized to give HP (Monks et al., 1992;Shackelford et al., 2000). It has been previously reported that exposure to HP or MD results in a cell cycle arrest (Flattery-O'Brien and Dawes, 1998;Leroy et al., 2001). However, the arrest points are not similar for the two agents. MD was reported to arrest cells at the G1 phase of the cell cycle, whereas HP was suggested to cause a G2 arrest by an alternate mechanism from that affected by MD (Flattery-O'Brien and Dawes, 1998); others reported that HP exposure causes a delay in the S phase (Leroy et al., 2001).Hundreds of genes are regulated so that they are expressed at specific times in the cell cycle and not at others (Cho et al., 1998;Spellman et al., 1998). The major part of this coordination is achieved by the sequential activation of a small number of transcription regulators (reviewed in Mendenhall and Hodge, 1998): MBF (a complex of Mbp1p and Swi6p) and SBF (a complex of Swi4p and Swi6p) are responsible for activating G1 transcription (Koch et al., 1993); Fkh1p and a complex formed by the cooperative promoter binding of Mcm1p and Fkh2p and a later recruitment of Ndd1p are responsible for activating G2/M transcription (Koranda et al., 2000;Kumar et al., 2000;Pic et al., 2000;Hollenhorst et al., 2001); Swi5p and Ace2p...

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Section: Discussionmentioning

confidence: 99%

Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress

Shapira

Segal

Botstein

2004

MBoC

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“…Interestingly, SelR is also a zinccontaining enzyme. 135 The metal is bound through four Cys residues, and has been suggested to play a structural function. 136 4.13.…”

Section: Selenoprotein Rmentioning

confidence: 99%

Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

589

409

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Despite its very low level in humans, selenium plays an important and unique role among the (semi)metal trace essential elements because it is the only one for which incorporation into proteins is genetically encoded, as the constitutive part of the 21st amino acid, selenocysteine. Twenty-five selenoproteins have been identified so far in the human proteome. The biological functions of some of them are still unknown, whereas for others there is evidence for a role in antioxidant defence, redox state regulation and a wide variety of specific metabolic pathways. In relation to these functions, the selenoproteins emerged in recent years as possible biomarkers of several diseases such as diabetes and several forms of cancer. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important requisite to elucidate its preventing/therapeutic effect for human diseases. This review summarizes the most recent findings on the biochemistry of active selenium species in humans, and addresses the latest evidence on the link between selenium intake, selenoproteins functionality and beneficial health effects. Primary emphasis is given to the interpretation of biochemical mechanisms rather than epidemiological/observational data. In this context, the review includes the following sections: (1) brief introduction; (2) general nutritional aspects of selenium; (3) global view of selenium metabolic routes; (4) detailed characterization of all human selenoproteins; (5) detailed discussion of the relation between selenoproteins and a variety of human diseases.

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“…The ability of yeast MsrA to reduce protein-bound Met-S-SO and the ability of MsrB to reduce Met-R-SO was determined by the reduction of dabsylated methionine sulfoxides to dabsylated methionine with an HPLC assay as described in ref. 11. Reaction mixtures had 5 g of purified enzymes and 25-400 M methionine sulfoxide substrates, and were incubated for 30 min before HPLC analysis.…”

Section: Possible Additional Component In the Yeast Methionine Sulfoxidementioning

confidence: 99%

Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen species-dependent and -independent components of aging

Koç

Gasch

Rutherford

et al. 2004

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

Self Cite

185

180

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Aging is thought to be caused by the accumulation of damage, primarily from oxidative modifications of cellular components by reactive oxygen species (ROS). Here we used yeast methionine sulfoxide reductases MsrA and MsrB to address this hypothesis. In the presence of oxygen, these antioxidants could increase yeast lifespan and did so independent of the lifespan extension offered by caloric restriction. However, under ROS-deficient, strictly anaerobic conditions, yeast lifespan was shorter, not affected by MsrA or MsrB, and further reduced by caloric restriction. In addition, we identified changes in the global gene expression associated with aging in yeast, and they did not include oxidative stress genes. Our findings suggest how the interplay between ROS, antioxidants, and efficiency of energy production regulates the lifespan. The data also suggest a model wherein factors implicated in aging (for example, ROS) may influence the lifespan yet not be the cause of aging.A ging is typically viewed as the accumulation of damage that results in death. This damage is thought to be caused by reactive oxygen species (ROS). Indeed, ROS can damage biomolecules, accelerate aging, and shorten lifespan (1-3), whereas antioxidant enzymes alleviate these effects, providing support for a free radical theory of aging (4). The contrasting effects of ROS and antioxidants, as well as correlation between accumulation of oxidative damage in cellular components and the lifespan of an organism, have been the main arguments in favor of this theory.Proteins become oxidatively damaged by oxidation of their amino acid residues and cofactors. Methionine residues in proteins are particularly susceptible to oxidation by ROS, resulting in methionine-S-sulfoxides (Met-S-SO) and methionine-R-sulfoxides (Met-R-SO) (5). Oxidized methionines can be repaired by antioxidant enzymes Met-S-SO reductase (MsrA) and Met-R-SO reductase (MsrB) (6). Recent studies revealed that methionine sulfoxide reduction provides lifespan extension in animals: deletion of the MsrA gene in mice reduced lifespan by Ϸ40% (7), whereas MsrA overexpression, predominantly in the nervous system, extended fruit fly lifespan by Ϸ70% (8). The correlation between methionine sulfoxide reductase activity and lifespan has been attributed to antioxidant function of MsrA. The role of MsrB in lifespan regulation has not been previously addressed.Most known modulators of the rate of aging are conserved across species, suggesting that common, conserved processes regulate and cause aging in diverse organisms. For example, caloric restriction (CR) is a dietary regimen that is known to extend lifespan in organisms from yeast to mammals (3, 9, 10). Saccharomyces cerevisiae has been extensively used as a model organism in studies on the mechanisms of aging (9, 10). Yeast express methionine sulfoxide reductases and can grow both aerobically and anaerobically, and in the present study, we used these features to examine the casual role of ROS-dependent processes in aging. Materials and MethodsYeas...

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Selenoprotein R is a zinc-containing stereo-specific methionine sulfoxide reductase

Cited by 246 publications

References 40 publications

Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress

Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress

Selenium biochemistry and its role for human health

Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen species-dependent and -independent components of aging

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