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Muscle Proteolysis (muscle + proteolysis)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Not All Injury-induced Muscle Proteolysis Is Due to Increased Activity of the Ubiquitin/Proteasome System: Evidence for Up-Regulation of Macrophage-associated Lysosomal Proteolysis in a Model of Local Trauma

NUTRITION REVIEWS, Issue 1 2003
Article first published online: 16 SEP 200
A characteristic response to injury is a dramatic loss of skeletal muscle protein owing to increased muscle protein breakdown. Over the past decade, numerous studies have indicated that up-regulaton of the ubiquitin-proteasome system is a common mechanism underlying such injury-induced muscle proteolysis. However, a recent study using a single-impact trauma to the gastrocnemius muscle found that, although the rate of muscle proteolysis was dramatically increased, the ubiquitin-proteasome system was not involved. Rather, an increase in lysosomal activity, through infiltration of the damaged tissue by mononuclear macrophages, is responsible for the high rates of protein breakdown. [source]

Heightened levels of circulating 20S proteasome in critically ill patients

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2005
G. A. Roth
Abstract Background, Recently, circulating proteasome core particles (20S proteasome) have been suggested as a marker of cell damage and immunological activity in autoimmune diseases. Aberrant leucocyte activation and increased lymphocyte apoptosis with consecutive T-cell unresponsiveness is deemed to play a pivotal role in the sepsis syndrome. Moreover sepsis-induced muscle proteolysis mainly reflects ubiqutin proteasome-dependent protein degradation. We therefore sought to investigate serum levels of 20S proteasome in critical ill patients. Material and methods, Case,control-study at a university hospital intensive care unit; 15 patients recruited within 24,48 h of diagnosis of sepsis, 13 trauma patients recruited within 24 h of admission to the ICU, a control group of 15 patients who underwent abdominal surgery, and 15 healthy volunteers. ELISA was used to measure the concentration of 20S proteasome in the sera of the patients and controls. Data are given as mean ± SEM. Mann,Whitney U -test was used to calculate significance and a P -value of 0·05 was considered to be statistically significant. Results, Marked increase of 20S proteasome was detected in the sera of septic patients (33 551 ± 10 034 ng mL,1) as well as in trauma patients (29 669 ± 5750 ng mL,1). In contrast, significantly lower concentrations were found in the abdominal surgery group (4661 ± 1767 ng mL,1) and in the healthy control population (2157 ± 273 ng mL,1). Conclusion, Detection of 20S proteasome may represent a novel marker of immunological activity and muscle degradation in sepsis and trauma patients, and may be useful in monitoring the clinical effect of proteasome-inhibitors. [source]

Molecular mechanisms activating muscle protein degradation in chronic kidney disease and other catabolic conditions

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2005
J. Du
Abstract Muscle atrophy is a prominent feature of chronic kidney disease (CKD) and is frequent in other catabolic conditions. Results from animal models of these conditions as well as patients indicate that atrophy is mainly owing to accelerated muscle proteolysis in the ubiquitin-proteasome (Ub-P'some) proteolytic system. The Ub-P'some system, however, rapidly degrades actin or myosin but cannot breakdown actomyosin or myofibrils. Consequently, another protease must initially cleave the complex structure of muscle. We identified caspase-3 as an initial and potentially rate-limiting proteolytic step that cleaves actomyosin/myofibrils to produce substrates degraded by the Ub-P'some system. In rodent models of CKD and other catabolic conditions, we find that caspase-3 is activated and cleaves actomyosin to actin, myosin and their fragments. This initial proteolytic step in muscle leaves a characteristic footprint, a 14-kDa actin band, providing a potential diagnostic tool to detect muscle catabolism. We also found that stimulation of caspase-3 activity depends on inhibition of IRS-1-associated phosphatidylinositol 3-kinase (PI3K) activity; inhibiting PI3K in muscle cells also leads to expression of a critical E3-ubiquitin-conjugating enzyme involved in muscle protein breakdown: atrogin-1/MAFbx. Thus, protein breakdown by caspase-3 and the ubiquitin-proteasome system in muscle are stimulated by the same signal: a low PI3K activity. These responses could yield therapeutic strategies to block muscle atrophy. [source]

Not All Injury-induced Muscle Proteolysis Is Due to Increased Activity of the Ubiquitin/Proteasome System: Evidence for Up-Regulation of Macrophage-associated Lysosomal Proteolysis in a Model of Local Trauma

NUTRITION REVIEWS, Issue 1 2003
Article first published online: 16 SEP 200
A characteristic response to injury is a dramatic loss of skeletal muscle protein owing to increased muscle protein breakdown. Over the past decade, numerous studies have indicated that up-regulaton of the ubiquitin-proteasome system is a common mechanism underlying such injury-induced muscle proteolysis. However, a recent study using a single-impact trauma to the gastrocnemius muscle found that, although the rate of muscle proteolysis was dramatically increased, the ubiquitin-proteasome system was not involved. Rather, an increase in lysosomal activity, through infiltration of the damaged tissue by mononuclear macrophages, is responsible for the high rates of protein breakdown. [source]