Document Detail

Alveolar extracellular 20S proteasome in patients with acute respiratory distress syndrome.
MedLine Citation:
PMID:  19286628     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Repair mechanisms resulting in alveolar protein degradation in acute respiratory distress syndrome (ARDS) are largely unknown. OBJECTIVES: To test whether the 20S proteasome is present and functional in the alveolar space in patients with ARDS. METHODS: Proteasome antigenic concentration in bronchoalveolar lavage (BAL) supernatants was measured by ELISA in patients with ARDS (n = 64), acute lung injury (ALI) (n = 8), sarcoidosis (n = 13), and in healthy subjects (n = 8). Cleavage of specific fluorogenic substrates (+/-epoxomicin), I(125) albumin degradation rate, and gel filtration were used to quantify and characterize proteasomal activity. The presence of proteasomes was confirmed independently by electron microscopic techniques. MEASUREMENTS AND MAIN RESULTS: Proteasome concentrations in patients with ARDS were markedly increased (1,069 +/- 1,194 ng/ml) in comparison to healthy subjects (60.8 +/- 49.8; P < 0.001), ALI (154 +/- 43; P = 0.006), and sarcoidosis (97.6 +/- 42.2; P = 0.037). All fluorogenic substrates were hydrolyzed (Suc-LLVY-AMC, 3.6 +/- 8.8 pkat/mg; BZ-VGR-AMC, 1.8 +/- 3.1; Suc-LLE-AMC, 1 +/- 1.7) by BAL supernatants of patients with ARDS, with inhibition by epoxomicin (P = 0.0001), and the majority of proteolytic activity was detected in BAL supernatant. Maximum hydrolyzing activity occurred at 660 kD and 20S proteasome was seen microscopically after purification and being released by pneumocytes type II. Proteasomal activity and albumin degradation rate in patients with ARDS were approximately 17-fold lower than in healthy subjects. Proteasomal activity in normal BAL was inhibited by BAL aliquots from patients with ARDS but not by denatured BAL, and returned to normal by purification. CONCLUSIONS: For the first time, we identified extracellular, biologically active 20S proteasome in the alveolar space of patients with ARDS in concentrations much higher than in normal subjects or in those with ALI.
Stephan Urs Sixt; Michael Adamzik; Daniel Spyrka; Boris Saul; Jan Hakenbeck; Jeremias Wohlschlaeger; Ulrich Costabel; Alexander Kloss; Jan Giesebrecht; Burkhardt Dahlmann; Jürgen Peters
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2009-03-12
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  179     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-05     Completed Date:  2009-06-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1098-106     Citation Subset:  AIM; IM    
Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Hufelandstrasse 55, Essen, Germany.
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MeSH Terms
Biological Markers / metabolism
Bronchoalveolar Lavage Fluid / chemistry
Disease Progression
Enzyme-Linked Immunosorbent Assay
Extracellular Fluid / enzymology*
Follow-Up Studies
Microscopy, Immunoelectron
Middle Aged
Prospective Studies
Proteasome Endopeptidase Complex / metabolism*
Pulmonary Alveoli / enzymology*,  ultrastructure
Respiratory Distress Syndrome, Adult / enzymology*,  epidemiology,  pathology
Risk Factors
Reg. No./Substance:
0/Biological Markers; EC Endopeptidase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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