Is the normal content of sulfhydryl groups attributable to sparing from dystrophic pathology in dystrophin-deficient muscles?
Deficiency of dystrophin in skeletal muscles is supposed to be responsible for all the symptoms associated with Duchenne dystrophy (DMD) and Becker dystrophy (BMD). The dystrophin-deficient mdx mice, however, are clinically almost asymptomatic. Hence, other factor(s) might be responsible for the muscle pathology in DMD and BDM. As sulfhydryl groups are involved in maintaining the structure of membranes and the protein-phospholipid interactions, total, protein-bound and free sulfhydryl groups (-SH) in DMD, BMD, limb-girdle dystrophy (LGMD) and the mdx mice muscles have been determined. A significant decrease of total and protein-bound -SH groups content and an increased proportion of free -SH groups in DMD and BMD was found. In LGMD the changes of total and protein-bound -SH groups content were less expressed. In the mdx mice muscles the content of -SH groups was generally normal, only a higher than normal proportion of free-SH groups content in old and senile animals, especially in their diaphragm, was present. To test the sarcolemmal integrity, albumin/creatine kinase (CK) influx/efflux was determined. In early stages of DMD and BMD the albumin influx was increased. In advanced stages of these diseases albumin influx was not observed. In LGMD albumin penetration was present only in a few fibres. CK efflux in vitro was increased both in early and advanced DMD cases. In BMD and LGMD CK efflux was increased only in early stages of the diseases. In mdx mice an increased influx/efflux of albumin/CK was stated in adult animals. The changes persisted in the mdx hind limb muscles up to the senile age of the animals. In the mdx diaphragm of senile animals albumin did not penetrate the muscle cell and no increase of CK efflux was observed. It is suggested that changes in the distribution of -SH groups take part in the molecular disorganisation of the sarcolemma in course dystrophinopathies. Normal content of the sulfhydryl groups is supposed to be attributable to sparing from dystrophic pathology in dystrophin-deficient mdx mice muscles.
Niebrój-Dobosz
Irena
I
Department of Neurology, Medical University, Warszawa, Poland.
Fidziańska
Anna
A
Glinka
Zofia
Z
Hausmanowa-Petrusewicz
Irena
I
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000418:Albumins / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D002648:Child; D002675:Child, Preschool; D003402:Creatine Kinase / Q000378:metabolism; D016189:Dystrophin / Q000172:deficiency*; D006801:Humans; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000378:metabolism; D009136:Muscular Dystrophies / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D012508:Sarcolemma / Q000737:chemistry / Q000473:pathology; D013045:Species Specificity; D013438:Sulfhydryl Compounds / Q000032:analysis*
D000418:Albumins; D016189:Dystrophin; D013438:Sulfhydryl Compounds; D003402:Creatine Kinase