title: The molecular basis of skeletal muscle atrophy.
abstract: Skeletal muscle atrophy attributable to muscular inactivity has significant adverse functional consequences. While the initiating physiological event leading to atrophy seems to be the loss of muscle tension and a good deal of the physiology of muscle atrophy has been characterized, little is known about the triggers or the molecular signaling events underlying this process. Decreases in protein synthesis and increases in protein degradation both have been shown to contribute to muscle protein loss due to disuse, and recent work has delineated elements of both synthetic and proteolytic processes underlying muscle atrophy. It is also becoming evident that interactions among known proteolytic pathways (ubiquitin-proteasome, lysosomal, and calpain) are involved in muscle proteolysis during atrophy. Factors such as TNF-alpha, glucocorticoids, myostatin, and reactive oxygen species can induce muscle protein loss under specified conditions. Also, it is now apparent that the transcription factor NF-kappaB is a key intracellular signal transducer in disuse atrophy. Transcriptional profiles of atrophying muscle show both up- and downregulation of various genes over time, thus providing further evidence that there are multiple concurrent processes involved in muscle atrophy. The purpose of this review is to synthesize our current understanding of the molecular regulation of muscle atrophy. We also discuss how ongoing work should uncover more about the molecular underpinnings of muscle wasting, particularly that due to disuse.
authors.affiliation: Boston University, Department of Health Sciences, 635 Commonwealth Ave., Rm. 443, Boston, MA 02215, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Jackman
authors.forename: Susan C
authors.initials: SC
authors.lastname: Kandarian
mesh_terms: D015870:Gene Expression; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000235:genetics / Q000503:physiopathology*; D020966:Muscular Disorders, Atrophic / Q000235:genetics / Q000503:physiopathology*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D009124:Muscle Proteins; D016328:NF-kappa B