Modulation of SERCA in the chronic phase of adjuvant arthritis as a possible adaptation mechanism of redox imbalance.
Adjuvant arthritis (AA) is a condition that involves systemic oxidative stress. Unexpectedly, it was found that sarcoplasmic reticulum Ca(2 +)-ATPase (SERCA) activity was elevated in muscles of rats with AA compared to controls, suggesting possible conformational changes in the enzyme. There was no alteration in the nucleotide binding site but rather in the transmembrane domain according to the tryptophan polar/non-polar fluorescence ratio. Higher relative expression of SERCA, higher content of nitrotyrosine but no increase in phospholipid oxidation in AA SR was found. In vitro treatments of SR with HOCl showed that in AA animals SERCA activity was more susceptible to oxidative stress, but SR phospholipids were more resistant and SERCA could also be activated by phosphatidic acid. It was concluded that increased SERCA activity in AA was due to increased levels of SERCA protein and structural changes to the protein, probably induced by direct and specific oxidation involving reactive nitrogen species.
Strosova
Miriam
M
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia.
Karlovska
Jana
J
Spickett
Corinne M
CM
Orszagova
Zuzana
Z
Ponist
Silvester
S
Bauerova
Katarina
K
Mihalova
Danica
D
Horakova
Lubica
L
D000222:Adaptation, Physiological; D000818:Animals; D001169:Arthritis, Experimental / Q000201:enzymology* / Q000382:microbiology / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002155:Calsequestrin / Q000378:metabolism; D002908:Chronic Disease; D007700:Kinetics; D015227:Lipid Peroxidation; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000503:physiopathology; D009161:Mycobacterium; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010712:Phosphatidic Acids / Q000378:metabolism; D050050:Protein Carbonylation; D011487:Protein Conformation; D051381:Rats; D011917:Rats, Inbred Lew; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation
C506945:Atp2a1 protein, rat; D002155:Calsequestrin; D010712:Phosphatidic Acids; C002744:3-nitrotyrosine; D014443:Tyrosine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium