Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis.

Patients with sepsis in the ICU (intensive care unit) are characterized by skeletal muscle wasting. This leads to muscle dysfunction that also influences the respiratory capacity, resulting in prolonged mechanical ventilation. Catabolic conditions are associated with a general activation of the ubiquitin-proteasome pathway in skeletal muscle. The aim of the present study was to measure the proteasome proteolytic activity in both respiratory and leg muscles from ICU patients with sepsis and, in addition, to assess the variation of proteasome activity between individuals and between duplicate leg muscle biopsy specimens. When compared with a control group (n=10), patients with sepsis (n=10) had a 30% (P<0.05) and 45% (P<0.05) higher proteasome activity in the respiratory and leg muscles respectively. In a second experiment, ICU patients with sepsis (n=17) had a 55% (P<0.01) higher proteasome activity in the leg muscle compared with a control group (n=10). The inter-individual scatter of proteasome activity was larger between the patients with sepsis than the controls. We also observed a substantial intra-individual difference in activity between duplicate biopsies in several of the subjects. In conclusion, the proteolytic activity of the proteasome was higher in skeletal muscle from patients with sepsis and multiple organ failure compared with healthy controls. It was shown for the first time that respiratory and leg muscles were affected similarly. Furthermore, the variation in proteasome activity between individuals was more pronounced in the ICU patients for both muscle types, whereas the intra-individual variation between biopsies was similar for ICU patients and controls.

[1]  C. Dejong,et al.  Increased expression of proteasome subunits in skeletal muscle of cancer patients with weight loss. , 2005, The international journal of biochemistry & cell biology.

[2]  C. Ottenheijm,et al.  Diaphragm dysfunction in chronic obstructive pulmonary disease. , 2005, American journal of respiratory and critical care medicine.

[3]  F. Hammarqvist,et al.  An assay of microsomal membrane-associated proteasomes demonstrates increased proteolytic activity in skeletal muscle of intensive care unit patients. , 2005, Clinical nutrition.

[4]  S. Powers,et al.  Trolox attenuates mechanical ventilation-induced diaphragmatic dysfunction and proteolysis. , 2004, American journal of respiratory and critical care medicine.

[5]  J. Wernerman,et al.  Effects on skeletal muscle of intravenous glutamine supplementation to ICU patients , 2004, Intensive Care Medicine.

[6]  B. Dahlmann,et al.  Alteration of 20S proteasome-subtypes and proteasome activator PA28 in skeletal muscle of rat after induction of diabetes mellitus. , 2003, The international journal of biochemistry & cell biology.

[7]  R. Dean,et al.  Assessment of proteasome activity in cell lysates and tissue homogenates using peptide substrates. , 2003, The international journal of biochemistry & cell biology.

[8]  M. Muscaritoli,et al.  Increased Muscle Proteasome Activity Correlates With Disease Severity in Gastric Cancer Patients , 2003, Annals of surgery.

[9]  S. Powers,et al.  Mechanical ventilation-induced diaphragmatic atrophy is associated with oxidative injury and increased proteolytic activity. , 2002, American journal of respiratory and critical care medicine.

[10]  A. Lucia,et al.  Immunolabelling, histochemistry and in situ hybridisation in human skeletal muscle fibres to detect myosin heavy chain expression at the protein and mRNA level , 2001, Journal of anatomy.

[11]  A. Goldberg,et al.  What do we really know about the ubiquitin-proteasome pathway in muscle atrophy? , 2001, Current opinion in clinical nutrition and metabolic care.

[12]  P. Kloetzel,et al.  Subtypes of 20S proteasomes from skeletal muscle. , 2001, Biochimie.

[13]  P. Hasselgren,et al.  Burn injury upregulates the activity and gene expression of the 20 S proteasome in rat skeletal muscle , 2000 .

[14]  G. Biolo,et al.  Contribution of the ubiquitin-proteasome pathway to overall muscle proteolysis in hypercatabolic patients. , 2000, Metabolism: clinical and experimental.

[15]  P. Essén,et al.  Protein-sparing effect in skeletal muscle of growth hormone treatment in critically ill patients. , 2000, Annals of surgery.

[16]  J. Fischer,et al.  The expression of genes in the ubiquitin-proteasome proteolytic pathway is increased in skeletal muscle from patients with cancer. , 1999, Surgery.

[17]  A. Goldberg,et al.  Proteasome active sites allosterically regulate each other, suggesting a cyclical bite-chew mechanism for protein breakdown. , 1999, Molecular cell.

[18]  J. Fischer,et al.  Activity and expression of the 20S proteasome are increased in skeletal muscle during sepsis. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[19]  Cerqueira Ep,et al.  Electromyographic study of the pectoralis major, serratus anterior and external oblique muscles during respiratory activity in humans. , 1999, Electromyography and clinical neurophysiology.

[20]  M. Tobin,et al.  Respiratory muscle dysfunction in mechanically-ventilated patients , 1998, Molecular and Cellular Biochemistry.

[21]  K. Andersson,et al.  Longitudinal changes of biochemical parameters in muscle during critical illness. , 1997, Metabolism: clinical and experimental.

[22]  D. Garrel,et al.  Activation of the ubiquitin pathway in rat skeletal muscle by catabolic doses of glucocorticoids. , 1997, The American journal of physiology.

[23]  T. Meyer,et al.  Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic pathway in human skeletal muscle. , 1997, The Journal of clinical investigation.

[24]  L. Phillips,et al.  Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin-proteasome proteolytic pathway by a mechanism including gene transcription. , 1996, The Journal of clinical investigation.

[25]  J. Vincent,et al.  The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure , 1996, Intensive Care Medicine.

[26]  B. Beaufrère,et al.  Increased mRNA levels for components of the lysosomal, Ca2+-activated, and ATP-ubiquitin-dependent proteolytic pathways in skeletal muscle from head trauma patients. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[27]  A. Goldberg,et al.  Increase in levels of polyubiquitin and proteasome mRNA in skeletal muscle during starvation and denervation atrophy. , 1995, The Biochemical journal.

[28]  K. Tanaka,et al.  Regulation of gene expression of proteasomes (multi-protease complexes) during growth and differentiation of human hematopoietic cells. , 1992, The Journal of biological chemistry.

[29]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. , 1992, Chest.

[30]  D. Downham,et al.  Distribution of different fibre types in human skeletal muscles Fibre type arrangement in m. vastus lateralis from three groups of healthy men between 15 and 83 years , 1983, Journal of the Neurological Sciences.

[31]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. 1992. , 2009, Chest.

[32]  J. Wang,et al.  Burn injury upregulates the activity and gene expression of the 20 S proteasome in rat skeletal muscle. , 2000, Clinical science.

[33]  P. Essén,et al.  Tissue protein synthesis rates in critically ill patients. , 1998, Critical care medicine.

[34]  J Lexell,et al.  Distribution of different fibre types in human skeletal muscles. 2. A study of cross-sections of whole m. vastus lateralis. , 1983, Acta physiologica Scandinavica.