Ca²⁺-ATPase of sarco/endoplasmic reticulum (SERCA) may be modified by imbalance of redox homeostasis. Modification of specific amino acid residues of the SERCA protein, but also of phospholipids surrounding the enzyme may induce conformational changes resulting in modulation of enzyme activity, thus influencing signal pathways. Conformational changes of SERCA play a role also in biological aging, in chronic contractile muscle activity, and ischemia.

Adjuvant arthritis (AA), an animal model of human rheumatoid arthritis (RA), is in contrast to RA reversible. Neither fragmentation nor aggregation of the SERCA protein was observed in rats in the course of AA. The decrease of SERCA activity recorded on day 21 after inducing AA could not be explained by loss of thiol groups but rather by protein carbonyl formation. Conformational changes related to tryptophan residues situated mainly in the transmembrane region appeared to be involved in the modulation of SERCA activity. Neither nucleotide binding site nor phospolipids of the sarcoplasmic reticulum surrounding SERCA were sensitive against possible redox imbalance in rats with AA.

In rats with AA, SERCA appears to be oxidized directly by oxidants and not by products of phospholipid oxidation. The transmembrane domain seems to be critical for conformational alterations of SERCA and enzyme activity modulation.

This study was supported by VEGA 2/0090/08, APVV-51-017905 and by COST action B35.