Repair of Oxidized Calmodulin by Methionine Sulfoxide Reductase Restores Ability To Activate the Plasma Membrane Ca-ATPase

Sun, Hongxiang; Gao, Jun; Ferrington, Deborah A.; Biesiada, Homigol; Williams, Todd D.; Squier, Thomas C.

doi:10.1021/bi981295k

Cited by 153 publications

(145 citation statements)

References 43 publications

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“…Thus one possibility is that met oxidation in some proteins is particularly crucial in determining the lifespan of an organism, and MSRA may act to protect these key proteins. For instance, met oxidation in calmodulin inhibits its ability to activate the plasma membrane Ca 2ϩ ATPase, and met oxidation in calmodulin progressively increases with age in the rat brain (27,48). This observation may explain the age-related changes in intracellular Ca 2ϩ homeostasis in neurons (49,50).…”

Section: Discussionmentioning

confidence: 97%

High-quality life extension by the enzyme peptide methionine sulfoxide reductase

Ruan

Tang

Chen

et al. 2002

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

403

281

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Cumulative oxidative damages to cell constituents are considered to contribute to aging and age-related diseases. The enzyme peptide methionine sulfoxide reductase A (MSRA) catalyzes the repair of oxidized methionine in proteins by reducing methionine sulfoxide back to methionine. However, whether MSRA plays a role in the aging process is poorly understood. Here we report that overexpression of the msrA gene predominantly in the nervous system markedly extends the lifespan of the fruit fly Drosophila. The MSRA transgenic animals are more resistant to paraquatinduced oxidative stress, and the onset of senescence-induced decline in the general activity level and reproductive capacity is delayed markedly. The results suggest that oxidative damage is an important determinant of lifespan, and MSRA may be important in increasing the lifespan in other organisms including humans.

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Section: Discussionmentioning

confidence: 97%

High-quality life extension by the enzyme peptide methionine sulfoxide reductase

Ruan

Tang

Chen

et al. 2002

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

403

281

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“…Repair of oxidized methionine has been shown to protect against oxidative stress in a number of cells, oxidation of methionine may lead to significant changes in protein structure and functions. Eight targets for MsrA have been reported including ribosomal protein L12 , α-1-proteinase inhibitor (Abrams et al, 1981), calmodulin (Sun et al, 1999), Ffh protein in E.coli (Ezraty et al, 2004), HIV-2 protease (Davies, et al, 2000), shaker potassium channel (Ciorba et al, 1997), Hsp 21 (Gustavssson et al, 2002 and recently α-synuclein (Liu et al, 2008) but it is thought that many more targets exist.…”

Section: The Methionine Sulfoxide Reductase Repair Systemmentioning

confidence: 99%

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Brennan¹,

Kantorow²

2009

Experimental Eye Research

158

139

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Oxidative stress occurs when the level of prooxidants exceeds the level of antioxidants in cells resulting in oxidation of cellular components and consequent loss of cellular function. Oxidative stress is implicated in wide range of age related disorders including Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis (ALS), Huntington's disease and the aging process itself (Lin and Beal, 2006). In the anterior segment of the eye, oxidative stress has been linked to lens cataract (Truscott, 2005) and glaucoma (Tezel, 2006) while in the posterior segment of the eye oxidative stress has been associated with macular degeneration (Hollyfield et al., 2008). Key to many oxidative stress conditions are alterations in the efficiency of mitochondrial respiration resulting in superoxide (O 2 -) production. Superoxide production precedes subsequent reactions that form potentially more dangerous reactive oxygen species (ROS) species such as the hydroxyl radical (˙OH), hydrogen peroxide (H 2 O 2 ) and peroxynitrite (OONO -). The major source of ROS in the mitochondria, and in the cell overall, is leakage of electrons from complexes I and III of the electron transport chain. It is estimated that 0.2-2% of oxygen taken up by cells is converted to ROS, through mitochondrial superoxide generation, by the mitochondria (Hansford et al., 1997). Generation of superoxide at complex I and III has been shown to occur at both the matrix side of the inner mitochondrial membrane and the cytosolic side of the membrane (Kakkar and Singh 2007). While exogenous sources of ROS such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins may contribute to the oxidative milieu, mitochondria are perhaps the most significant contribution to ROS production affecting the aging process. In addition to producing ROS, mitochondria are also a target for ROS which in turn reduces mitochondrial efficiency and leads to the generation of more ROS in a vicious self-destructive cycle. Consequently, the mitochondria have evolved a number of antioxidant and key repair systems to limit the damaging potential of free oxygen radicals and to repair damaged proteins (Figure 1.0). The aging eye appears to be at considerable risk from oxidative stress. This review will outline the potential role of mitochondrial function and redox balance in age-related eye diseases, and detail how the methionine sulfoxide reductase (Msr)

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“…A sample of α-synuclein pretreated with H 2 O 2 was incubated for 2 h at 37 °C with recombinant, bovine MsrA in the presence of DTT, which served as an electron donor for MetSO repair [49]. Following the incubation, α-synuclein eluted from the RP-HPLC column as three major peaks, referred to as peaks 1, 2, and 3 in order of their retention times ( Figure 8C).…”

Section: Msra Repairs Oxidized α-Synuclein In Cell-free Systemsmentioning

confidence: 99%

Methionine sulfoxide reductase A protects dopaminergic cells from Parkinson's disease-related insults

Liu

Hindupur

Nguyen

et al. 2008

Free Radical Biology and Medicine

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Parkinson's disease (PD) is a neurologic disorder characterized by dopaminergic cell death in the substantia nigra. PD pathogenesis involves mitochondrial dysfunction, proteasome impairment, and α-synuclein aggregation, insults that may be especially toxic to oxidatively stressed cells including dopaminergic neurons. The enzyme methionine sulfoxide reductase A (MsrA) plays a critical role in the antioxidant response by repairing methionine-oxidized proteins and by participating in cycles of methionine oxidation and reduction that have the net effect of consuming reactive oxygen species. Here, we show that MsrA suppresses dopaminergic cell death and protein aggregation induced by the complex I inhibitor rotenone or mutant α-synuclein, but not by the proteasome inhibitor MG132. By comparing the effects of MsrA and the small-molecule antioxidants N-acetyl-cysteine and vitamin E, we provide evidence that MsrA protects against PD-related stresses primarily via methionine sulfoxide repair rather than by scavenging reactive oxygen species. We also demonstrate that MsrA efficiently reduces oxidized methionine residues in recombinant α-synuclein. These findings suggest that enhancing MsrA function may be a reasonable therapeutic strategy in PD. Keywords aggresome; dopamine; glutathione; heat shock protein; methionine sulfoxide reductase; neurodegeneration; oxidative stress; Parkinson's disease; proteasome; protofibril; rotenone; synuclein Parkinson's disease (PD) is a neurologic disorder that involves a selective loss of dopaminergic neurons from the substantia nigra [1,2]. The postmortem brains of PD patients are characterized by reduced activity of mitochondrial complex I, an enzyme of the mitochondrial electron transport chain [3,4]. In turn, this defect may cause a 'leakage' of electrons from mitochondria, leading to the accumulation of reactive oxygen species (ROS) that damage *Corresponding author. Address: Jean-Christophe Rochet, Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, RHPH 410A, West Lafayette, Indiana, 47907-209147907- . Fax: 765-494-1414. E-mail: rochet@pharmacy.purdue.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptFree Radic Biol Med. Author manuscript; available in PMC 2009 August 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript proteins, lipids, and nucleic acids [3,5]. The brains of PD patients also show evidence of impaired proteasomal function [6], a defect that results in increased oxidative stress and decreased elimination...

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Repair of Oxidized Calmodulin by Methionine Sulfoxide Reductase Restores Ability To Activate the Plasma Membrane Ca-ATPase

Cited by 153 publications

References 43 publications

High-quality life extension by the enzyme peptide methionine sulfoxide reductase

High-quality life extension by the enzyme peptide methionine sulfoxide reductase

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Methionine sulfoxide reductase A protects dopaminergic cells from Parkinson's disease-related insults

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