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62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

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Extracellular biologically active proteasome in cebrebrospinal fluid: a novel function for a well-known protein?

Meeting Abstract

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  • O.M. Müller - Klinik für Neurochirurgie, Universitätsklinikum Essen
  • J. Wiedemann - Klinik für Neurochirurgie, Universitätsklinikum Essen
  • T. Anlasik - Klinik für Anästhesie und Intensivmedizin, Heinrich-Heine-Universität Düsseldorf
  • J. Thomassen - Klinik für Anästhesie und Intensivmedizin, Heinrich-Heine-Universität Düsseldorf
  • S. Sixt - Klinik für Anästhesie und Intensivmedizin, Heinrich-Heine-Universität Düsseldorf
  • U. Sure - Klinik für Neurochirurgie, Universitätsklinikum Essen

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocP 052

doi: 10.3205/11dgnc273, urn:nbn:de:0183-11dgnc2735

Published: April 28, 2011

© 2011 Müller et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: To prove the existence and biological function of the free extracellular proteasome in the cerebrospinal fluid (CSF). The proteasome’s substrate ubiquitin has been proven to be biologically active in CSF. We hypothesized that the proteasome can also be found in the CSF, as in the e.g. human alveolar space.

Methods: The present study was granted by the local ethics research council board. CSF samples from a total of 30 patients in the neurosurgical department, who underwent lumbar puncture for diagnostic myelography, were analyzed for total cell count, lactate, glucose, total protein content and IL-6 concentration. The concentration of the extracellular proteasome (EP) was measured in the supernatant of CSF using ELISA. Biological activity of EP was assessed by measuring the hydrolyzing activities with the fluorogenic substrate Suc-LLVY-AMC. For potential inhibition of EP activity epoximicin (Calbiochem, San Diego, CA) was added. Electron microscopy (EM) of the choroid plexus was performed in search of transportation mechanisms for proteasomes.

Results: EP was demonstrated in all probes. EP activity could be proven in all CSF samples, as well. Inhibition of the hydrolyzing activity by epoxomicin was highly significant (p<0.001). There was no correlation between the concentration of proteasome in the blood serum and CSF, which rules out the hypothesis that EP in the CSF is an ultrafiltrated substrate only. EM of the plexus epithelial tissue revealed vesicles containing antibody-reactive proteasome, suggesting exocytosis of the proteasome in the extracellular space.

Conclusions: EP in the CSF is described for the first time. Biological activity of EP and its inhibition are demonstrated. We hypothesize that the proteasome is transported at the choroid plexus into the CSF by means of exocytosis due to a – so far – unknown activation process. Further investigations will focus on EP concentrations in neoplastic or neurodegenerative diseases and inflammatory conditions (SAH, vasospasm).