title: Involvement of autophagic degradation in ACTH-induced skeletal muscle atrophy.
abstract: Intracellular autophagic breakdown was investigated in skeletal myocytes undergoing atrophy under the influence of ACTH. Adult male Sprague-Dawley rats received s.c. injections of ACTH (12.5 U/kg body wt) or physiological saline as control twice daily. 5 experimental and 5 control animals were sacrificed by perfusion fixation after 6, 9, and 12 days of treatment. While the weight of the left pectoralis minor muscle decreased significantly in the ACTH-treated animals compared with controls, the volume fraction of autophagic vacuoles, as determined by quantitative electron microscopy, increased significantly after 9 days (2.6-fold) and 12 days (2.9-fold) in the atrophying skeletal myocytes of experimental animals compared with controls. Only non-myofibrillar components were detected as contents of autophagic vacuoles. Since, however, the ratio of myofibrils to other cytoplasmic components remained constant, the degradation of myofibrils seems to occur via a non-lysosomal pathway. The data suggest that the breakdown of cytoplasmic components by cellular autophagy is important for the development of skeletal muscle atrophy as observed following long-term ACTH treatment or in Cushing's syndrome.
authors.affiliation: Department of Psychiatry, Central Institute of Mental Health, Mannheim, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bahro
authors.forename: U
authors.initials: U
authors.lastname: Pfeifer
authors.forename: J
authors.initials: J
authors.lastname: Dämmrich
mesh_terms: D000324:Adrenocorticotropic Hormone; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D003593:Cytoplasm / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009132:Muscles / Q000187:drug effects / Q000648:ultrastructure*; D009133:Muscular Atrophy / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014617:Vacuoles / Q000648:ultrastructure
chemical_list: D000324:Adrenocorticotropic Hormone