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Methionine Sulfoxide Reductase (methionine + sulfoxide_reductase)

Distribution by Scientific Domains

Life Sciences	80%

Selected Abstracts

Methionine sulfoxide reductase A expression is regulated by the DAF-16/FOXO pathway in Caenorhabditis elegans

AGING CELL, Issue 6 2009
Alicia N. Minniti
Summary The methionine sulfoxide reductase system has been implicated in aging and protection against oxidative stress. This conserved system reverses the oxidation of methionine residues within proteins. We analyzed one of the components of this system, the methionine sulfoxide reductase A gene, in Caenorhabditis elegans. We found that the msra-1 gene is expressed in most tissues, particularly in the intestine and the nervous system. Worms carrying a deletion of the msra-1 gene are more sensitive to oxidative stress, show chemotaxis and locomotory defects, and a 30% decrease in median survival. We established that msra-1 expression decreases during aging and is regulated by the DAF-16/FOXO3a transcription factor. The absence of this enzyme decreases median survival and affects oxidative stress resistance of long lived daf-2 worms. A similar effect of MSRA-1 absence in wild-type and daf-2 (where most antioxidant enzymes are activated) backgrounds, suggests that the lack of this member of the methionine repair system cannot be compensated by the general antioxidant response. Moreover, FOXO3a directly activates the human MsrA promoter in a cell culture system, implying that this could be a conserved mechanism of MsrA regulation. Our results suggest that repair of oxidative damage in proteins influences the rate at which tissues age. This repair mechanism, rather than the general decreased of radical oxygen species levels, could be one of the main determinants of organisms' lifespan. [source]

3242: MsrA repair of Cytochrome c and ,-crystallin links chaperone and oxidative repair pathways with mitochondrial protection and apoptotic control in lens cells.

ACTA OPHTHALMOLOGICA, Issue 2010
M KANTOROW
Purpose Methionine sulfoxide reductase A (MsrA) is essential for lens defense against oxidative stress and cataract formation through its ability to repair oxidized protein methionine (PMSO). Here, we examined ,-crystallin and cytochrome c (Cyt c) as potential targets for MsrA-repair in the lens. Methods The oxidized methionine content of ,-crystallin and Cyt c was evaluated from the lenses of MsrA knockout and w+ mice. The activities of ,,crystallin and Cyt c were evaluated upon methionine oxidation. The ability of MsrA to repair these proteins and restore their respective chaperone and electron transport activities was determined. All three proteins were localized in lens cells and their abilities to form complexes in vitro and in vivo evaluated. Results Cyt c was oxidized at met 80 and ,,-crystallin at met 68 in MsrA-knockout relative to w+ mice. Methionine oxidization of 138 of ,A-crystallin and 68 of ,B-crystallin resulted in loss of ,-crystallin chaperone function while oxidation of met 80 resulted in loss of Cyt c electron transport function. ,-crystallin protected Cyt c against methioinine oxidation. MsrA repaired and restored the functions of all three proteins which co-localized and formed complexes in lens mitochondria. Conclusion MsrA is likely required for repair of ,-crystallin and Cyt c in lens cells suggesting that it maintains and regulates the activities of ,-crystallin and Cyt c in lens mitochondria where all three proteins were localized. Loss of MsrA-repair could contribute to cataract formation through loss of chaperone function, loss of oxidative phosphorylation and/or increased Cyt c mediated apoptosis. [source]

Protein modification and replicative senescence of WI-38 human embryonic fibroblasts

AGING CELL, Issue 2 2010
Emad K. Ahmed
Summary Oxidized proteins as well as proteins modified by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE) and by glycation (AGE) have been shown to accumulate with aging in vivo and during replicative senescence in vitro. To better understand the mechanisms by which these damaged proteins build up and potentially affect cellular function during replicative senescence of WI-38 fibroblasts, proteins targeted by these modifications have been identified using a bidimensional gel electrophoresis-based proteomic approach coupled with immunodetection of HNE-, AGE-modified and carbonylated proteins. Thirty-seven proteins targeted for either one of these modifications were identified by mass spectrometry and are involved in different cellular functions such as protein quality control, energy metabolism and cytoskeleton. Almost half of the identified proteins were found to be mitochondrial, which reflects a preferential accumulation of damaged proteins within the mitochondria during cellular senescence. Accumulation of AGE-modified proteins could be explained by the senescence-associated decreased activity of glyoxalase-I, the major enzyme involved in the detoxification of the glycating agents methylglyoxal and glyoxal, in both cytosol and mitochondria. This finding suggests a role of detoxification systems in the age-related build-up of damaged proteins. Moreover, the oxidized protein repair system methionine sulfoxide reductase was more affected in the mitochondria than in the cytosol during cellular senescence. Finally, in contrast to the proteasome, the activity of which is decreased in senescent fibroblasts, the mitochondrial matrix ATP-stimulated Lon-like proteolytic activity is increased in senescent cells but does not seem to be sufficient to cope with the increased load of modified mitochondrial proteins. [source]

Methionine sulfoxide reductase A expression is regulated by the DAF-16/FOXO pathway in Caenorhabditis elegans

Methionine sulphoxide reductase is an important antioxidant enzyme in the gastric pathogen Helicobacter pylori

MOLECULAR MICROBIOLOGY, Issue 5 2004
Praveen Alamuri
Summary The ability of Helicobacter pylori to colonize the stomach requires that it combat oxidative stress responses imposed by the host. The role of methionine sulfoxide reductase (Msr), a methionine repair enzyme, in H. pylori stress resistance was evaluated by a mutant analysis approach. An msr mutant strain lacked immunologically detectable sulphoxide reductase protein and also showed no enzyme activity when provided with oxidized methionines as substrates. The mutant strain showed diminished growth compared to the parent strain in the presence of chemical oxidants, and showed rapid viability loss when exposed to oxidizing conditions. The stress resistance and enzyme activity could be recovered by complementing the mutant with a functional copy of the msr gene. Upon fractionation of parent strain and the complemented mutant cells into membranes and cytoplasmic proteins, most of the immunologically detectable Msr was localized to the membrane, and this fraction contained all of the Msr activity. Qualitative detection of the whole cell protein pattern using 2,4-dinitro phenyl hydrazine (DNPH) showed a far greater number of oxidized protein species in the mutant than in the parent strain when the cells were subjected to oxygen, peroxide or s-nitrosoglutathione (GSNO) induced stress. Importantly, no oxidized proteins were discerned in either strain upon incubation in anaerobic conditions. A mutant strain that synthesized a truncated Msr (corresponding to the MsrA domain) was slightly more resistant to oxidative stress than the msr strain. Mouse colonization studies showed Msr is an important colonization factor, especially for effective longer-term (14 and 21 days) colonization. Complementation of the mutant msr strain by chromosomal insertion of a functional gene restored mouse colonization ability. [source]