Modulation of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase activity and oxidative modification during the development of adjuvant arthritis

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Abstract

Adjuvant arthritis (AA) was induced by intradermal administration of Mycobacterium butyricum to the tail of Lewis rats. In sarcoplasmic reticulum (SR) of skeletal muscles, we investigated the development of AA. SR Ca(2+)-ATPase (SERCA) activity decreased on day 21, suggesting possible conformational changes in the transmembrane part of the enzyme, especially at the site of the calcium binding transmembrane part. These events were associated with an increased level of protein carbonyls, a decrease in cysteine SH groups, and alterations in SR membrane fluidity. There was no alteration in the nucleotide binding site at any time point of AA, as detected by a FITC fluorescence marker. Some changes observed on day 21 appeared to be reversible, as indicated by SERCA activity, cysteine SH groups, SR membrane fluidity, protein carbonyl content and fluorescence of an NCD-4 marker specific for the calcium binding site. The reversibility may represent adaptive mechanisms of AA, induced by higher relative expression of SERCA, oxidation of cysteine, nitration of tyrosine and presence of acidic phospholipids such as phosphatidic acid. Nitric oxide may regulate cytoplasmic Ca(2+) level through conformational alterations of SERCA, and decreasing levels of calsequestrin in SR may also play regulatory role in SERCA activity and expression.

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Original languageEnglish
Pages (from-to)40-47
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume511
Issue number1-2
Early online date22 Apr 2011
DOIs
Publication statusPublished - Jul 2011

    Keywords

  • animals, experimental arthritis, carrier proteins, membrane fluidity, skeletal muscle, oxidative stress, phosphatidic acids, protein carbonylation, protein conformation, post-translational protein processing, rats, inbred Lew rats, sarcoplasmic reticulum, sarcoplasmic reticulum calcium-transporting ATPases, sulfhydryl compounds, SERCA, free radicals, calsequestrin, nitrotyrosine, adjuvant arthritis

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