ELEVATED LEVELS OF A CALCIUM-ACTIVATED MUSCLE PROTEASE IN RAPIDLY ATROPHYING MUSCLES FROM VITAMIN-E-DEFICIENT RABBITS

A Ca2+-activated proteolytic enzyme that partially degrades myofibrils was isolated from hind limb muscles of normal rabbits and rabbits undergoing rapid muscle atrophy due to vitamin E deficiency. Extractable Ca2+-activated protease activity was 3.6 .times. higher in muscle tissue from vitamin E-deficient rabbits than from muscle tissue of control rabbits. Ultrastructural studies of muscle from vitamin E-deficient rabbits showed that the Z disc was the 1st myofibrillar structure to show degradative changes in atrophying muscle. Myofibrils prepared from muscles from vitamin E-deficient rabbits showed partial or complete loss of Z-disc density. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that the amount of troponin-T (37,000 daltons) and .alpha.-actinin (96,000 daltons) was less in myofibrils from atrophying muscle than in myofibrils prepared from control muscle. In vitro treatment of purified myofibrils with purified Ca2+-activated proteolytic enzyme produced alterations in myofibrillar ultrastructure that were identical to the initial alterations occurring in myofibrils from atrophying muscle (i.e., weakening and subsequent removal of Z discs). The electrophoretic banding pattern of Ca2+-activated proteolytic enzyme-treated myofibrils is very similar to that of myofibrils prepared from muscles atrophying as a result of nutritional vitamin E deficiency. The possible role of Ca2+-activated proteolytic enzyme in disassembly and degradation of the myofibril is discussed.