Serum CK, calcium, magnesium, and oxidative phosphorylation in mdx mouse muscular dystrophy

Abstract

Serum creatine kinase (CK) activity, calcium (Ca) and magnesium (Mg) contents of skeletal muscle and isolated mitochondria, as well as oxidative phosphorylation of X-linked muscular dystrophic (mdx) mice were compared with normal control animals at ages 5, 10, and 23 weeks. Serum CK is elevated in mdx mice at all ages, with highest activities at 5 weeks. The Ca content of dystrophic skeletal muscle is increased at all ages, whereas no clearly abnormal trend in muscle Mg levels was observed. Noncollagen protein (NCP), which was used as a reference base, is significantly diminished in muscle from 10- and 23-week-old mdx animals. Isolated mitochondria from mdx mice have elevated calcium content and decreased respiratory control ratios with NAD-linked substrates pyruvate/malate. The findings are distinct from those in dystrophic mice, strain 129/ReJ, but similar to observations in dystrophic hamsters and Duchenne muscular dystrophy and reflect the occurrence of overt muscle cell necrosis.

Expression of the glucose transporter GLUT4 in the muscular dystrophic mdx mouse

“…In accord with previous reports, the mdx mice did not show striking alterations in development [1,10], with their mean body weight even being increased compared with control mice at 6-7 months of age [30]. High activities of the muscular enzyme creatine kinase were present in the serum of mdx compared with control mice, as previously described [1,[31][32][33]. This measurement was used in our study to confirm the phenotype of each mouse.…”

The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice

“…Although muscle fibers degenerate in the absence of myotubularin, sarcolemmal integrity remains mostly conserved, as opposed to several muscular dystrophies. Accordingly, blood levels of CK in Mtm1 KO mice are only slightly elevated in late stages of the disease, inflammatory infiltrates and fibrosis are absent in muscle, and regenerating myotubes are infrequent and nongrouped, which contrast with observations in mouse models of Duchenne muscular dystrophy (35,44) or in other dystrophic mice (36). These results suggest that myotubularin plays a role either in regulating signals from the extracellular compartment needed for muscle cell function or in preserving the internal architecture of myofibers.…”

Protein turnover is elevated in muscle of mdx mice in vivo

“…It seems likely that the elevated protein turnover observed in mdx mouse muscles is a consequence of their being subject to a continued process of damage and repair, a suggestion which is supported by the histological observation of numerous degenerating and regenerating fibres in these muscles [14].…”

“…Current evidence indicates that the increased intracellular Ca2+ content of mdx muscle fibres [14,15] may initiate the myopathic events. It has been demonstrated that the Ca2+ ionophore A23 187 causes increased proteolysis [16] and induces damage to muscle of normal mice and rats [17] through mechanisms which may involve activation of phospholipase enzymes [18].…”