Heightened levels of circulating 20S proteasome in critically ill patients

Roth, Georg A.; Moser, Bernhard; Krenn, Claus G.; Roth‐Walter, Franziska; Hetz, Hubert; Richter, Susanne; Brunner, Markus; Jensen‐Jarolim, Erika; Wolner, Ernst; Höetzenecker, Konrad; Boltz-Nitulescu, G; Ankersmit, Hendrik Jan

doi:10.1111/j.1365-2362.2005.01508.x

Cited by 64 publications

(66 citation statements)

References 22 publications

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“…Thus, the origin, the cellular extrusion mechanism(s), and the functions of extracellular, circulating proteasomes remain enigmatic. Nevertheless, their concentration is a useful diagnostic criterion for disease activity in patients with various illnesses (2)(3)(4)(5)(6). Our investigation showed that the pattern of subtypes of circulating proteasomes is changed in patients with SLE and RA compared with controls, and this change may somehow reflect the disease state of the donors and may be the basis for development of a new diagnostic test system to detect disease and monitor therapy.…”

Section: Discussionmentioning

confidence: 85%

“…High-resolution anion exchange chromatography (in conjunction with a SMART chromatography system; Amersham Biosciences) was used to separate 20S proteasome subtypes on a Mini Q anion exchange column equilibrated with TEAD buffer as described elsewhere (6 ).…”

Section: Analysis Of Proteasome Subtypesmentioning

confidence: 99%

“…Wada et al (2 ) used ELISA to measured the concentrations of circulating proteasomes in sera from patients with hematologic malignancies and with various liver diseases and found that they were substantially higher than circulating proteasome in plasma of healthy patients. Similarly increased concentrations of circulating proteasomes were detected in plasma of patients with solid tumors, myeloproliferative and myelodysplastic syndromes (4 ), various autoimmune diseases (3 ), metastatic malignant melanoma or severe psoriasis (5 ), and critical illness with sepsis and trauma (6 ). Chemotherapeutic treatment of patients with acute leukemia decreased or even normalized concentrations of circulating proteasomes (2,4 ).…”

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confidence: 99%

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Circulating Proteasomes Are Functional and Have a Subtype Pattern Distinct from 20S Proteasomes in Major Blood Cells

et al. 2006

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Background: 20S proteasomes, the proteolytic core particles of the major intracellular protein degradative pathway, are potential disease markers because they are detectable in human plasma as circulating proteasomes and their concentrations are increased in patients suffering from various diseases. To investigate the origin of circulating proteasomes, we compared some of their features with those of proteasomes isolated from major blood cells. Methods: We isolated circulating proteasomes from the plasma of 2 patients with rheumatoid arthritis and 2 with systemic lupus erythematosus and from human plasma from healthy donors. We purified the proteasomes to apparent homogeneity and then used electron microscopy for imaging and chromatography for subtype spectrum analysis. We compared subtype results with those from 20S proteasomes purified from 4 major blood cell populations. We also tested proteasomes for enzymatic activity and immunosubunit content. Results: Circulating proteasomes from plasma of healthy donors and from patients with autoimmune disease were found to have the same size and shape as erythrocyte proteasomes, be proteolytically active, and contain standard-and immunosubunits. Chromatography revealed 6 circulating proteasome subtype peaks in healthy donor plasma and 7 in patient donor plasma. Proteasomes from erythrocytes had 3 subtype peaks and

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Section: Discussionmentioning

confidence: 85%

Section: Analysis Of Proteasome Subtypesmentioning

confidence: 99%

mentioning

confidence: 99%

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Circulating Proteasomes Are Functional and Have a Subtype Pattern Distinct from 20S Proteasomes in Major Blood Cells

et al. 2006

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“…20S proteasomes are also detectable in healthy serum and plasma, and elevated circulating 20S proteasome (c20S) concentrations have been described in several diseases, such as hematologic malignancies, sepsis, trauma, and autoimmune diseases including systemic lupus erythematosus (SLE) (5,13,15,16). Although evidence for the functional role of c20S has not yet been provided, systemic concentrations of c20S are thought to reflect cellular damage and immunological activity.…”

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confidence: 99%

Circulating 20S Proteasome Levels in Patients with Mixed Connective Tissue Disease and Systemic Lupus Erythematosus

Majetschak

Perez

Sorell

et al. 2008

Clin Vaccine Immunol

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“…A small case-control study of critically ill patients found signifi cantly higher serum levels of 20S proteasome in 15 patients admitted to the ICU with a diagnosis of sepsis and 13 with a diagnosis of trauma compared with 15 patients admitted for elective abdominal surgery and 15 healthy volunteers. 79 A mouse model of sepsis found that infusion of the proteasome inhibitor MG-132 signifi cantly dampened tumor necrosis factor-a , IL-1, and IL-10 levels and prolonged survival compared with placebo. 80 This fi nding may suggest that circulating proteasome interacts with the infl ammatory response in sepsis, implying that the proteasome may have important immunomodulatory functions in patients with critical illness such as sepsis.…”

Section: Extracellular Proteasome Function In Sepsis and Alimentioning

confidence: 99%

Ubiquitination and Proteolysis in Acute Lung Injury

Vadász

Weiss

Sznajder

2012

Chest

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CHEST The Ubiquitin Proteasome SystemThe Discovery of the Ubiquitin Proteasome System P rotein turnover plays an important role in a broad spectrum of cellular processes. Notably, approximately 3% to 5% of our cellular proteins are degraded and resynthesized daily. 1 Until the mid-1970s it was widely believed that all intracellular proteins were degraded at the same rate in lysosomes in a nonspecifi c manner, despite the fact that proteins have a wide range of half-lives. 1 The existence of a novel, highly regulated, and specifi c degradation pathway was fi rst proposed by Ciechanover and colleagues 2 and Hershko and colleagues, 3 which was in agreement with the discovery of an ATP-dependent proteolytic system in reticulocytes that lack lysosomes. 4 As it was described 2 years later, this novel degradation pathway was mediated by a small protein of 76 amino acid residues, termed ATP-dependent proteolysis factor-1 or ubiquitin. 5 , 6 The Ubiquitin Enzymatic Cascade During ubiquitination, target proteins become "marked" as ubiquitin covalently conjugates via its C-terminal glycine to protein substrates at the ´ -amino group of their lysine residues. 7 Conjugation of ubiquitin to a target protein occurs via an enzymatic cascade. 1 , 7 Ubiquitin is fi rst activated by an ATP-dependent E1 ubiquitin-activating enzyme by the formation of a thiolester bond between the E1 enzyme and ubiquitin. Ubiquitin is then transferred via a transthiolation Ubiquitination is a posttranslational modifi cation that regulates a variety of cellular functions depending on timing, subcellular localization, and type of tagging, as well as modulators of ubiquitin binding leading to proteasomal or lysosomal degradation or nonproteolytic modifi cations. Ubiquitination plays an important role in the pathogenesis of acute lung injury (ALI) and other lung diseases with pathologies secondary to infl ammation, mechanical ventilation, and decreased physical mobility. Particularly, ubiquitination has been shown to affect alveolar epithelial barrier function and alveolar edema clearance by targeting the Na,K-ATPase and epithelial Na 1 channels upon lung injury. Notably, the proteasomal system also exhibits distinct functions in the extracellular space, which may contribute to the pathogenesis of ALI and other pulmonary diseases. Better understanding of these mechanisms may ultimately lead to novel therapeutic modalities by targeting elements of the ubiquitination pathway.CHEST 2012; 141( 3 ): 763 -771Abbreviations : ALI 5 acute lung injury ; ARDS 5 acute respiratory distress syndrome ; ELF 5 epithelial lining fl uid ; ENaC 5 epithelial Na 1 channels ; NEDD8 5 neural precursor cell expressed, developmentally downregulated 8 ; pVHL 5 von Hippel Lindau protein; RING 5 really interesting new gene

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Heightened levels of circulating 20S proteasome in critically ill patients

Abstract: 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.

Cited by 64 publications

References 22 publications

Circulating Proteasomes Are Functional and Have a Subtype Pattern Distinct from 20S Proteasomes in Major Blood Cells

Circulating Proteasomes Are Functional and Have a Subtype Pattern Distinct from 20S Proteasomes in Major Blood Cells

Circulating 20S Proteasome Levels in Patients with Mixed Connective Tissue Disease and Systemic Lupus Erythematosus

Ubiquitination and Proteolysis in Acute Lung Injury

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