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

Majetschak, Matthias; Perez, Monica A.; Sorell, Luis; Lam, J.; Maldonado, Marcos; Hoffman, Robert W.

doi:10.1128/cvi.00187-08

Cited by 32 publications

(32 citation statements)

References 13 publications

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“…Nevertheless, because 20S proteasome BALF concentrations were found to be significantly lower in patients who were distinguishable from ARDS patients only by a higher P/F ratio (> 200 mmHg and ≤ 300 mmHg) and thus, were grouped as patients with acute lung injury (14, 30), it appears that increases in BALF proteasome concentrations require a certain threshold of acute lung damage, that may not have been reached in patients with ALI. Although the exact cellular origin of proteasomes in the systemic circulation or in BALF is unknown, current findings on proteasomes in BALFs along with previous observations on circulating proteasomes in conditions that are associated with increased cell damage (9, 11, 13) collectively point towards passive release from destroyed or damaged cells and tissues. On the other hand, proteasomes have recently been observed in vacuoles adjacent to cell membrane of pneumocytes type II, and thus, may also be released into the BALF from exocytotic vesicles (14).…”

Section: Discussionmentioning

confidence: 68%

“…Besides the intracellular localization of proteasomes, the 20S proteasome is also a constituent of normal plasma and increased concentrations of circulating 20S proteasomes have been reported under various pathological conditions, including autoimmune diseases, trauma and sepsis (5–11). While evidence for a functional role of circulating 20S proteasomes has as yet not been provided, it is thought to reflect the extent of cell damage and immunological activity in disease states (9–11).…”

Section: Introductionmentioning

confidence: 99%

“…While evidence for a functional role of circulating 20S proteasomes has as yet not been provided, it is thought to reflect the extent of cell damage and immunological activity in disease states (9–11). …”

Section: Introductionmentioning

confidence: 99%

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Proteasomes in Human Bronchoalveolar Lavage Fluid After Burn and Inhalation Injury

Albright

Romero

Saini

et al. 2009

Journal of Burn Care & Research

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Objective To determine whether 26S proteasome is detectable in human bronchoalveolar-lavage fluid (BALF) and whether burn and inhalation injury is accompanied by changes in BALF proteasome content or activity. Methods BALF was obtained on hospital admission from 28 patients with burn and inhalation injury (controls: 10 healthy volunteers). Proteasome concentrations were quantified by ELISA and their native molecular mass was assessed by gel filtration. Proteasome peptidase activity was measured employing a chymotryptic-like peptide substrate in combination with epoxomicin (specific proteasome inhibitor). Results BALF protein was increased in patients (p<0.001) and correlated positively with the degree of inhalation injury. 20S/26S proteasomes were detectable in all BALF by ELISA. Gel filtration confirmed the presence of intact 20S and of 26S proteasome which was stable without soluble ATP/Mg2+. In all BALF chymotryptic-like activity was detectable and could be inhibited with epoxomicin by 60–70% (p<0.01). Absolute amounts of 20S/26S proteasomes and proteasome activity were increased in patients (p<0.001 for all). The relative BALF composition after injury was characterized by increased concentrations of 20S proteasome/mg protein (p=0.0034 vs. volunteers), decreased concentrations of 26S proteasome/mg protein (p=0.041 vs. volunteers) and reduced specific proteasome activity (p=0.044 vs. volunteers). 26S proteasome/mg and specific proteasome activity were even further reduced in patients who developed ventilator-associated pneumonia (p=0.045 and p=0.03 vs. patients without VAP, respectively). Conclusions The present study supports the novel concept that extracellular proteasomes could play a pathophysiological role in the injured lung and suggests that insufficient proteasome function may increase susceptibility for pulmonary complications.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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Proteasomes in Human Bronchoalveolar Lavage Fluid After Burn and Inhalation Injury

Albright

Romero

Saini

et al. 2009

Journal of Burn Care & Research

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“…Показано, что в ответ на различные воздействия происходит перераспределение протеасом в клетке [159][160][161]. Более того, при различных стрессовых воздействиях, например, при разного рода повреждениях или заболеваниях, включая различные формы рака, существенно увеличивается число внеклеточных 20S протеасом (в сыворотке крови, спинномозговой жидкости, жидкости бронхоальвеолярного лаважа) [162][163][164][165][166][167][168].…”

Section: способы регуляции убиквитин-независимой протеасомной деградацииunclassified

Ubiquitin-independent protein degradation in proteasomes

Buneeva

Медведев

2018

BIOMED KHIM

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Proteasomes are large supramolecular protein complexes present in all prokaryotic and eukaryotic cells, where they perform targeted degradation of intracellular proteins. Until recently, it was generally accepted that prior proteolytic degradation in proteasomes the proteins had to be targeted by ubiquitination: the ATP-dependent addition of (typically four sequential) residues of the low-molecular ubiquitin protein, involving the ubiquitin-activating enzyme, ubiquitin-conjugating enzyme and ubiquitin ligase. The cytoplasm and nucleoplasm proteins labeled in this way are then digested in 26S proteasomes. However, in recent years it has become increasingly clear that using this route the cell eliminates only a part of unwanted proteins. Many proteins can be cleaved by the 20S proteasome in an ATP-independent manner and without previous ubiquitination. Ubiquitin-independent protein degradation in proteasomes is a relatively new area of studies of the role of the ubiquitin-proteasome system. However, recent data obtained in this direction already correct existing concepts about proteasomal degradation of proteins and its regulation. Ubiquitin-independent proteasome degradation needs the main structural precondition in proteins: the presence of unstructured regions in the amino acid sequences that provide interaction with the proteasome. Taking into consideration that in humans almost half of all genes encode proteins that contain a certain proportion of intrinsically disordered regions, it appears that the list of proteins undergoing ubiquitin-independent degradation will demonstrate further increase. Since 26S of proteasomes account for only 30% of the total proteasome content in mammalian cells, most of the proteasomes exist in the form of 20S complexes. The latter suggests that ubiquitin-independent proteolysis performed by the 20S proteasome is a natural process of removing damaged proteins from the cell and maintaining a constant level of intrinsically disordered proteins. In this case, the functional overload of proteasomes in aging and/or other types of pathological processes, if it is not accompanied by triggering more radical mechanisms for the elimination of damaged proteins, organelles and whole cells, has the most serious consequences for the whole organism.

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“…The PA700 regulator binds to the outer a-rings of the 20S core and, also according to Ostrowska et al [4], the 'resulting 26S proteasome is responsible for energy-dependent degradation of polyubiquitinated proteins, including many short-lived regulatory proteins that control cell cycle progression, apoptosis, signal transduction, and gene expression' [5]. In humans, extracellular proteasomes have been found circulating in the plasma of patients suffering from a wide range of inflammatory autoimmune diseases and with neoplasms [6][7][8][9][10][11]. It is already known that the level of proteasomes correlate with the severity of the disease in different pathologies [12].…”

Section: Introductionmentioning

confidence: 99%

Immunoproteasome in the blood plasma of children with acute appendicitis, and its correlation with proteasome and UCHL1 measured by SPR imaging biosensors

Matuszczak

Sankiewicz

Dębek

et al. 2017

Clinical and Experimental Immunology

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SummaryThe aim of this study was to determinate the immunoproteasome concentration in the blood plasma of children with appendicitis, and its correlation with circulating proteasome and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1). Twenty-seven children with acute appendicitis, managed at the Paediatric Surgery Department, were included randomly into the study (age 2 years 9 months up to 14 years, mean age 9Á5 6 1 years). There were 10 girls and 17 boys; 18 healthy, age-matched subjects, admitted for planned surgeries served as controls. Mean concentrations of immunoproteasome, 20S proteasome and UCHL1 in the blood plasma of children with appendicitis before surgery 24 h and 72 h after the appendectomy were higher than in the control group. The immunoproteasome, 20S proteasome and UCHL1 concentrations in the blood plasma of patients with acute appendicitis were highest before surgery. The immunoproteasome, 20S proteasome and UCHL1 concentration measured 24 and 72 h after the operation decreased slowly over time and still did not reach the normal range (P < 0Á05). There was no statistical difference between immunoproteasome, 20S proteasome and UCHL1 concentrations in children operated on laparoscopically and children after classic appendectomy. The immunoproteasome concentration may reflect the metabolic response to acute state inflammation, and the process of gradual ebbing of the inflammation may thus be helpful in the assessment of the efficacy of treatment. The method of operation -classic open appendectomy or laparoscopic appendectomy -does not influence the general trend in immunoproteasome concentration in children with appendicitis.

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

Cited by 32 publications

References 13 publications

Proteasomes in Human Bronchoalveolar Lavage Fluid After Burn and Inhalation Injury

Proteasomes in Human Bronchoalveolar Lavage Fluid After Burn and Inhalation Injury

Ubiquitin-independent protein degradation in proteasomes

Immunoproteasome in the blood plasma of children with acute appendicitis, and its correlation with proteasome and UCHL1 measured by SPR imaging biosensors

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