Phospholipid composition and metabolism in mouse muscular dystrophy

Abstract

1. The composition and metabolism of phospholipids were studied in various tissues from both normal and dystrophic mice of the 129 ReJ strain. Phospholipids extracted from forebrain, spinal cord, sciatic nerve and plasma were fractionated by t.l.c. and measured. 2. Very significant alterations were found in the choline phospholipids from these tissues, except forebrain. Plasma phosphatidylcholine in the dystrophic mouse was increased by 38%. There was a 2-fold increase in lysophosphatidylcholine in the spinal cord of dystrophic mice. The sciatic nerve showed a marked decrease in sphingomyelin content, which is approximately half of that in the controls. 3. Five enzymes involved in phosphatidylcholine metabolism [namely cholinephosphotransferase (EC 2.7.8.2); phospholipases A (EC 3.1.1.4, EC 3.1.1.32); lysophospholipase (EC 3.1.1.5); lysophosphatidylcholine acyltransferase (EC 2.3.1.23); phospholipase C (EC 3.1.4.3)] were studied in tissue preparations from forebrain, spinal cord, sciatic nerves, gastrocnemius muscles and liver. 4. Activities of phospholipases A and C were significantly increased, about 5-fold and 60% respectively, in gastrocnemius muscle of dystrophic mice compared with controls. Phospholipases A also showed 50% higher activity in the sciatic nerves of dystrophic than of normal mice. Lysophosphatidylcholine acyltransferase activities were significantly increased in the sciatic nerves and spinal cord, by 50-100% over that of the controls. The forebrain and spinal cord from dystrophic mice, however, had only 60% of lysophospholipase activities of that of the normal control. Cholinephosphotransferase activity was unchanged in these tissues from both normal and dystrophic mice. 5. It is suggested that are number of features of mouse muscular dystrophy related to altered membrane structure and function can be rationalized in terms of changes in lipid composition and metabolism.