Muscle cachexia: current concepts of intracellular mechanisms and molecular regulation
PO Hasselgren, JE Fischer - Annals of surgery, 2001 - journals.lww.com
PO Hasselgren, JE Fischer
Annals of surgery, 2001•journals.lww.comSummary Background Data Muscle cachexia, mainly reflecting degradation of myofibrillar
proteins, is an important clinical feature in patients with severe injury, sepsis, and cancer.
The catabolic response in skeletal muscle may result in muscle wasting and weakness,
delaying or preventing ambulation and rehabilitation in these patients and increasing the
risk for pulmonary complications. Results Muscle cachexia, induced by severe injury, sepsis,
and cancer, is associated with increased gene expression and activity of the calcium/calpain …
proteins, is an important clinical feature in patients with severe injury, sepsis, and cancer.
The catabolic response in skeletal muscle may result in muscle wasting and weakness,
delaying or preventing ambulation and rehabilitation in these patients and increasing the
risk for pulmonary complications. Results Muscle cachexia, induced by severe injury, sepsis,
and cancer, is associated with increased gene expression and activity of the calcium/calpain …
Summary Background Data Muscle cachexia, mainly reflecting degradation of myofibrillar proteins, is an important clinical feature in patients with severe injury, sepsis, and cancer. The catabolic response in skeletal muscle may result in muscle wasting and weakness, delaying or preventing ambulation and rehabilitation in these patients and increasing the risk for pulmonary complications.
Results Muscle cachexia, induced by severe injury, sepsis, and cancer, is associated with increased gene expression and activity of the calcium/calpain-and ubiquitin/proteasome-proteolytic pathways. Calcium/calpain-regulated release of myofilaments from the sarcomere is an early, and perhaps rate-limiting, component of the catabolic response in muscle. Released myofilaments are ubiquitinated in the N-end rule pathway, regulated by the ubiquitin-conjugating enzyme E2 14k and the ubiquitin ligase E3α, and degraded by the 26S proteasome.
Conclusions An understanding of the mechanisms regulating muscle protein breakdown is important for the development of therapeutic strategies aimed at treating or preventing muscle cachexia in patients with severe injury, sepsis, cancer, and perhaps other catabolic conditions as well.
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