Molecular cloning and functional expression of a human peptide methionine sulfoxide reductase (hMsrA)

Kuschel, Lioba; Hansel, Alfred; Schönherr, Roland; Weissbach, Herbert; Brot, Nathan; Hoshi, Toshinori; Heinemann, Stefan H.

doi:10.1016/s0014-5793(99)00917-5

Cited by 110 publications

(109 citation statements)

References 16 publications

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“…This contrasts with all animal and microbial genomes described to date, which only contain a single pmsr gene (Kuschel et al, 1999). The relatively large number of pmsr genes in Arabidopsis is particularly significant, since it has one of the smallest genomes (120 Mb) of any higher eukaryote (Meinke et al, 1998).…”

Section: Discussionmentioning

confidence: 92%

Differential Regulation of Plastidial and Cytosolic Isoforms of Peptide Methionine Sulfoxide Reductase in Arabidopsis

et al. 2000

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We report the characterization of two members of a gene family from Arabidopsis that encode, respectively, cytosolic (cPMSR) and plastid-targeted (pPMSR) isoforms of the oxidative-stress-repair enzyme peptide methionine sulfoxide reductase. Overexpression of these proteins in Escherichia coli confirmed that each had PMSR enzyme activity with a synthetic substrate,N-acetyl-[3H]-methionine sulfoxide, or a biological substrate, α-1 proteinase inhibitor. The pPMSR was imported into intact chloroplasts in vitro with concomitant cleavage of its approximately 5-kD N-terminal signal peptide. The two PMSR isoforms exhibited divergent pH optima, tissue localization, and responses to developmental and environmental effects. Analysis of the Arabidopsis database indicated that there are probably at least twop-pmsr-like genes and three c-pmsr-like genes in the Arabidopsis genome. Expression of thep-pmsr genes and their protein products was restricted to photosynthetic tissues and was strongly induced following illumination of etiolated seedlings. In contrast, thec-pmsr genes were expressed at moderate levels in all tissues and were only weakly affected by light. Exposure to a variety of biotic and abiotic stresses showed relatively little effect onpmsr gene expression, with the exception of leaves subjected to a long-term exposure to the cauliflower mosaic virus. These leaves showed a strong induction of the c-pmsrgene after 2 to 3 weeks of chronic pathogen infection. These data suggest novel roles for PMSR in photosynthetic tissues and in pathogen defense responses in plants.

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Section: Discussionmentioning

confidence: 92%

Differential Regulation of Plastidial and Cytosolic Isoforms of Peptide Methionine Sulfoxide Reductase in Arabidopsis

et al. 2000

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“…The short form of MsrA lacks the mitochondrial sequence, but the cysteine-containing sequence and thioredoxin domain are active. Expression of MsrA is found in almost all human tissues with the exception of leukemia and lymphoma cell lines [39] . MsrA is specific for the reduction of free and protein-based methionine-S-sulfoxide in mammals [10,40] .…”

Section: Msrs: Gene Structure and Isoformsmentioning

confidence: 99%

Methionine sulfoxide reductase A: Structure, function and role in ocular pathology

Sreekumar¹

2011

WJBC

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Methionine is a highly susceptible amino acid that can be oxidized to S and R diastereomeric forms of methionine sulfoxide by many of the reactive oxygen species generated in biological systems. Methionine sulfoxide reductases (Msrs) are thioredoxin-linked enzymes involved in the enzymatic conversion of methionine sulfoxide to methionine. Although MsrA and MsrB have the same function of methionine reduction, they differ in substrate specificity, active site composition, subcellular localization, and evolution. MsrA has been localized in different ocular regions and is abundantly expressed in the retina and in retinal pigment epithelial (RPE) cells. MsrA protects cells from oxidative stress. Overexpression of MsrA increases resistance to cell death, while silencing or knocking down MsrA decreases cell survival; events that are mediated by mitochondria. MsrA participates in protein-protein interaction with several other cellular proteins. The interaction of MsrA with α-crystallins is of utmost importance given the known functions of the latter in protein folding, neuroprotection, and cell survival. Oxidation of methionine residues in α-crystallins results in loss of chaperone function and possibly its antiapoptotic properties. Recent work from our laboratory has shown that MsrA is co-localized with αA and αB crystallins in the retinal samples of patients with age-related macular degeneration. We have also found that chemically induced hypoxia regulates the expression of MsrA and MsrB2 in human RPE cells. Thus, MsrA is a critical enzyme that participates in cell and tissue protection, and its interaction with other proteins/growth factors may provide a target for therapeutic strategies to prevent degenerative diseases.

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“…MSRA typically derives its reducing power using electrons from the thioredoxin system in vivo or DTT in vitro (Moskovitz et al, 1996). SMLC itself is not an electron donor that the MSRA system can readily use to perform the reduction reaction (data not shown) as measured by the matrix-assisted laser desorption/ionization-based assay (Kuschel et al, 1999). Thus, the enhanced protection against oxidative stress only when cytoplasmic MSRA is present is consistent with the idea that SMLC enhances the efficacy of the MSRA catalytic antioxidant system by increasing the number of substrate molecules available.…”

Section: Open Circles Uas-␣-synuclein/ Ddc-gal4; Filled Circles Uasmentioning

confidence: 99%

Methionine Sulfoxide Reductase A and a Dietary SupplementS-Methyl-L-Cysteine Prevent Parkinson's-Like Symptoms

Wassef¹,

Haenold²,

Hansel³

et al. 2007

J. Neurosci.

115

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Parkinson's disease (PD), a common neurodegenerative disease, is caused by loss of dopaminergic neurons in the substantia nigra. Although the underlying cause of the neuronal loss is unknown, oxidative stress is thought to play a major role in the pathogenesis of PD. The amino acid methionine is readily oxidized to methionine sulfoxide, and its reduction is catalyzed by a family of enzymes called methionine sulfoxide reductases (MSRs). The reversible oxidation-reduction cycle of methionine involving MSRs has been postulated to act as a catalytic antioxidant system protecting cells from oxidative damage. Here, we show that one member of the MSR family, MSRA, inhibits development of the locomotor and circadian rhythm defects caused by ectopic expression of human ␣-synuclein in the Drosophila nervous system. Furthermore, we demonstrate that one way to enhance the MSRA antioxidant system is dietary supplementation with S-methyl-L-cysteine (SMLC), found abundantly in garlic, cabbage, and turnips. SMLC, a substrate in the catalytic antioxidant system mediated by MSRA, prevents the ␣-synuclein-induced abnormalities. Therefore, interventions focusing on the enzymatic reduction of oxidized methionine catalyzed by MSRA represent a new prevention and therapeutic approach for PD and potentially for other neurodegenerative diseases involving oxidative stress.

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Molecular cloning and functional expression of a human peptide methionine sulfoxide reductase (hMsrA)

Cited by 110 publications

References 16 publications

Differential Regulation of Plastidial and Cytosolic Isoforms of Peptide Methionine Sulfoxide Reductase in Arabidopsis

Differential Regulation of Plastidial and Cytosolic Isoforms of Peptide Methionine Sulfoxide Reductase in Arabidopsis

Methionine sulfoxide reductase A: Structure, function and role in ocular pathology

Methionine Sulfoxide Reductase A and a Dietary SupplementS-Methyl-L-Cysteine Prevent Parkinson's-Like Symptoms

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