Modulation of SERCA in the chronic phase of adjuvant arthritis as a possible adaptation mechanism of redox imbalance

Abstract

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.

Modern Pharmacological Approaches to Therapies: Substances Tested in Animal Models of Rheumatoid Arthritis

“…As resulted also from our previous experiments (Bauerova et al, 2005a, 2005b, 2008a, 2008bDrafi et al, 2010;Jancinova et al, 2009;Kogan et al, 2005;Macickova et al, 2010;Ponist et al, 2010;Sotnikova et al, 2009;Strosova et al, 2008Strosova et al, , 2009), all performed in the AA model, substances with antioxidant properties have a high potency to be used in therapy of RA. They decreased the progression of AA when administered to rats with AA over the period of 28 days.…”

“…Clinical studies have shown increased plasmatic levels of MDA in patients with RA (Baskol et al, 2005(Baskol et al, , 2006Sarban et al, 2005). The level of MDA in the plasma of arthritic animals was also elevated (Bauerova et al, 2008bHe et al, 2006;Sotnikova et al, 2009;Strosova et al, 2008Strosova et al, , 2009Tastekin et al, 2007). In recent years, methods based on chemiluminescence and fluorescence measurements have been widely used for determination of ROS, RNS and lipid peroxidation metabolites.…”

“…In this study, the content of carbonyls in the arthritic animals increased significantly in comparison with healthy controls and protein carbonyl determination in plasma was performed according to the method described by (Levine et al, 1990) and modified in agreement with the previously applied experimental conditions . Also in the following experiments with AA we found significant damage of proteins caused by oxidative stress accompanying arthritis (Bauerova et al, 2005b;Strosova et al, 2009). In addition to determination of protein carbonyls in plasma, we performed an assay of carbonyls in brain tissue and applied it as a marker of antioxidative properties of carnosine evaluated for monotherapy of AA .…”

Pharmacological influence on processes of adjuvant arthritis: effect of the combination of an antioxidant active substance with methotrexate

“…Bauerova and Bezek (1999) and Jaswal et al (2003) described oxidative stress as a primary factor involved in the RA pathogenetic changes. Our previous results with different antioxidants and immunomodulators showed a beneficial effect of these substances on the development of adjuvant arthritis (AA) (Bauerova et al , 2005a, 2005b 2008a, 2008b 2009, 2011, Drabikova et al , 2009; Drafi et al , 2010; Jancinova et al , 2009; Kogan et al , 2005; Macickova et al , 2010; Ponist et al , 2010; Sotnikova et al , 2009; Strosova et al , 2008, 2009). The advantage of AA as an experimental arthritis model is its great similarity to RA, such as symmetrical joint involvement, persistent joint inflammation, synovial hyperplasia, and a good response to most therapies effective in RA (Bina & Wilder, 1999).…”

Role of <i>Bifidobacterium bifidum</i> and plant food extracts in improving microflora and biochemical and cytogenetic parameters in adjuvant arthritis.

“…The increase in SOD induced the scavenging of the superoxide ione into H 2 O 2 , a more potent reactive oxygen species, which may be accumulated due to a reduction in GPx resulting in increased lipid peroxidation which is reflected in the significant increase in MDA in the present study. Adjuvant arthritis is a condition that involves systemic oxidative stress (Strosova et al, 2009), which could be reflected by an elevation in SOD and a reduction in GPx levels in the present study, together with the reduction in TAC and increased MDA. The elevation in the plasma levels of MDA in the arthritic control rats in the current research is in agreement with the results of Tastekin et al (2007).…”