Influence on Myoadenylate Deaminase Function in Rat Skeletal Muscle After Homologous and Heterologous Immunization With the Purified Enzyme

Abstract

The aim of the study was to shed some light on the possibility of anti-MAD autoantibodies in cases of rhabdomyolysis or microtraumatic muscular damage causing the symptoms of the acquired myoadenylate deaminase deficiency. Therefore a homologous and a heterologus immunization of rats was carried out with myoadenylate deaminase (MAD; EC 3.5.4.6.) isolated from rat white gastrocnemius muscle (type IIb) and rabbit skeletal muscle. Antibody response to homologous and heterologous antigens was quantified by ELISA and by the inhibition of MAD activity in vitro. Anti-MAD IgG antibodies obtained by homologous immunization caused an inhibition rate of 80% when using MAD from rat white gastrocnemius muscle. Furthermore, the function of MAD in homologously and heterologously immunized rats was investigated after maximal swimming exercise in comparison to non-immunized animals by determination of muscle ammonia and by HPLC detection of inosine 5'-monophosphate (IMP) in skeletal muscle tissues. Both IMP and ammonia accumulation were significantly reduced in type lib muscle fibers after homologous immunization of rats compared to non-immunized controls (n = 7), whereas the concentration of muscle lactate showed no differences. According to these results we propose that by homologous immunization with purified MAD, anti-MAD IgG impairs the function of cytoplasmic MAD during vigorous exercise in vivo.

Key words

Myoadenylate deaminase - myoadenylate deaminase deficiency - homologous and heterologous immunization