Glucocorticoid excess induces preferential depletion of myosin in denervated skeletal muscle fibers.
The combined effects of dexamethasone treatment (1 mg/Kg/day) plus denervation (DEX-DEN), were studied at 7, 13, and 28 days by microscopic, biochemical, and physiological techniques in plantaris and soleus muscles of adult rats. The results were compared with corresponding dexamethasone-treated (DEX) and denervated (DEN) muscles and appropriate controls. There was a significantly more marked atrophy of all fiber types in the DEX-DEN plantares at 7 and 13 days than in either DEX or DEN muscles. The degree of atrophy was greatest in type 2B fibers in DEX-DEN plantares. Electron microscopy revealed a severe preferential depletion of thick myofilaments in DEX-DEN plantares and solei but not in DEX or DEN muscles. The thick myofilament depletion in DEX-DEN muscles occurred in addition to a severe overall reduction of myofibrillar caliber. Gel electrophoresis showed a marked preferential decrease of myosin heavy chain in DEX-DEN plantares and solei, but not in either DEX or DEN muscles. Myosin light chains were also markedly reduced in DEX-DEN plantares and solei. In vitro physiological studies showed a marked reduction of the denervation-induced twitch potentiation in DEX-DEN solei. Maximal tetanic tension (20 Hz stimulation) per gram weight of muscle as well as the twitch-tetanus ratio was significantly reduced only in DEX-DEN solei in relation to controls. Myosin depletion in DEX-DEN muscles may be due to a severe preferential inhibition of its synthesis coupled with an accelerated catabolism.
D000199:Actins / Q000378:metabolism; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D008970:Molecular Weight; D009119:Muscle Contraction / Q000187:drug effects; D009121:Muscle Denervation; D009132:Muscles / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009218:Myosins / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000199:Actins; D003907:Dexamethasone; D009218:Myosins