Activity and isozyme pattern of lysosomal enzyme in skeletal muscle of patients with neuromuscular diseases
Yoneda, K.; Kawai, H.; Naruo, T.; Saito, S.
Shikoku Acta Medica 47(2-3): 59-71
The source of activated lysosomal enzymes in the skeletal muscles of the patients with neuromuscular diseases was studied by measuring the activities and isozyme patterns of the enzymes using biopsy specimens of the skeletal muscles. The subjects included 6 Duchenne muscular dystrophy (DMD), 3 myotonic dystrophy (MyD), 3 mitochondrial myopathy (MtM), 6 polymyositis (PM), 3 Charcot-Marie-Tooth disease (CMT), 5 amyotrophic lateral sclerosis (ALS), and 4 disuse atrophy (DUA). In addition, myoglobin content in the muscle, the ratio of the enzyme activity in the leukocytes (L) and skeletal muscles (M) (L/M) and pH dependent isozyme patterns of .alpha.-mannosidase and .alpha.-glucosidase were investigated. The results obtained were as follows: Myoglobin contents in the muscles of the patients with DMD were markedly decreased by 16% in normal muscles (6.7 .+-. 1.8 mg/g wet wt), and those of the patients with MyD, PM, ALS and DUA were reduced to 52% to 78%. The activities of almost all the enzymes were significantly increased to 1.8-4.1 times of the normal muscles in DMD and MyD muscles. Especially, remarkable increase was observed in the activiites of the enzymes with high L/M ratios (147-56) such as .alpha.-mannosidase, .beta.-galactosidase, .beta.-glucuronidase etc., which are contained much in the leukocytes. Similar results were obtained in the muscles of PM. On the other hand, the activities of .alpha.-fucosidase and .alpha.-glucosidase with low L/M ratio of 5 or 4 were significantly increased to 1.8-3.2 times of normal muscles in the patients with ALS and DUA. The activities of almost all the enzymes were within normal range in the muscles of MtM and CMT. The pH dependent isozyme patterns of .alpha.-mannosidase in the muscle of DMD resembled that in the leukocytes. The N/A ratio was as low as 1.2 to 0.5 compared with 5.0 in normal muscles. On the other hand, the patterns in the muscles of ALS and DUA resembled that of normal muscles. The N/A ratios of these two diseases were 6.1 and 6.4, respectively. The isozyme pattern of .alpha.-glucosidase was similar in normal muscles, leukocytes and the muscles of DMD and DUA. These data indicate that main source of the lysosomal enzymes in the skeletal muscles of the patients with DMD, MyD or PM is the phagocytic cells which infiltrate into the muscle tissue. However, in the skeletal muscles of the patients with ALS or DUA the lysosomal enzymes are activated by the intramyofibrial autophagic lysosomal system. It is also suggested that the increase in lysosomal enzyme activities in the diseased muscles is related to the disease itself, but not to the grade of muscle damage, because Mb contents, which show the muscle damage, are not correlated with the enzyme activities.