Linked Life Data

9890888

Source:http://linkedlifedata.com/resource/pubmed/id/9890888

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-2-18
pubmed:abstractText
We have investigated the ability of methionine sulfoxide reductase (MsrA) to maintain optimal calmodulin (CaM) function through the repair of oxidized methionines, which have been shown to accumulate within CaM in senescent brain [Gao, J., Yin, D. H., Yao, Y., Williams, T. D., and Squier, T. C. (1998) Biochemistry 37, 9536-9548]. Oxidatively modified calmodulin (CaMox) isolated from senescent brain or obtained by in vitro oxidation was incubated with MsrA. This treatment restores the functional ability of CaMox to activate the plasma membrane (PM) Ca-ATPase, confirming that (i) the decreased ability of CaM isolated from senescent animals to activate the PM Ca-ATPase results solely from methionine sulfoxide formation and (ii) MsrA can repair methionine sulfoxides within cytosolic proteins. We have used electrospray ionization mass spectrometry to investigate the extent and rates of methionine sulfoxide repair within CaMox. Upon exhaustive repair by MsrA, there remains a distribution of methionine sulfoxides within functionally reactivated CaMox, which varies from three to eight methionine sulfoxides. The rates of repair of methionine sulfoxides within individual tryptic fragments of CaMox vary by a factor of 2, where methionine sulfoxides located within hydrophobic sequences are repaired in preference to methionines that are more solvent accessible within the native structure. However, no single methionine sulfoxide is completely repaired in all CaM oxiforms. Decreases in the alpha-helical content and a disruption of the tertiary structure of CaM have previously been shown to result from methionine oxidation. Repair of selected methionine sulfoxides in CaMox by MsrA results in a partial refolding of the secondary structure, suggesting that MsrA repairs methionine sulfoxides within unfolded sequences until native-like structure and function are re-attained. The ability of CaMox isolated from senescent brain to fully activate the PM Ca-ATPase following repair by MsrA suggests the specific activity of MsrA is insufficient to maintain CaM function in aging brain. These results are discussed in terms of the possible regulatory role MsrA may play in the modulation of CaM function and calcium homeostasis under conditions of oxidative stress.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
105-12
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:9890888-Aging, pubmed-meshheading:9890888-Amino Acid Sequence, pubmed-meshheading:9890888-Animals, pubmed-meshheading:9890888-Brain, pubmed-meshheading:9890888-Calcium-Transporting ATPases, pubmed-meshheading:9890888-Calmodulin, pubmed-meshheading:9890888-Cell Membrane, pubmed-meshheading:9890888-Chromatography, High Pressure Liquid, pubmed-meshheading:9890888-Enzyme Activation, pubmed-meshheading:9890888-Mass Spectrometry, pubmed-meshheading:9890888-Methionine, pubmed-meshheading:9890888-Methionine Sulfoxide Reductases, pubmed-meshheading:9890888-Molecular Sequence Data, pubmed-meshheading:9890888-Oxidation-Reduction, pubmed-meshheading:9890888-Oxidoreductases, pubmed-meshheading:9890888-Peptide Fragments, pubmed-meshheading:9890888-Protein Folding, pubmed-meshheading:9890888-Protein Isoforms, pubmed-meshheading:9890888-Rats, pubmed-meshheading:9890888-Rats, Inbred F344, pubmed-meshheading:9890888-Trypsin
pubmed:year
1999
pubmed:articleTitle
Repair of oxidized calmodulin by methionine sulfoxide reductase restores ability to activate the plasma membrane Ca-ATPase.
pubmed:affiliation
Department of Molecular Biosciences, Mass Spectrometry Laboratory, University of Kansas, Lawrence 66045-2106, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.