Hilmar Nils Kühlein, Irmgard Tegeder, Christine Verena Möser, Hee-Young Lim, Annett Häussler, Katharina Spieth, Ingo Wilhelm Matthias Jennes, Rolf Marschalek, Tobias Beckhaus, Michael Karas, Markus Fauth, Corina Ehnert, Gerd Geisslinger, Ellen Niederberger
- Nerve injury leads to sensitization mechanisms in the peripheral and central nervous system which involve transcriptional and post-transcriptional modifications in sensory nerves. To assess protein regulations in the spinal cord after injury of the sciatic nerve in the Spared Nerve Injury model (SNI) we performed a proteomic analysis using 2D-difference gel electrophoresis (DIGE) technology. Among approximately 2300 protein spots separated on each gel we detected 55 significantly regulated proteins after SNI whereof 41 were successfully identified by MALDI-TOF MS. Out of the proteins which were regulated in the DIGE analyses after SNI we focused on the carboxypeptidase A inhibitor latexin because protease dysfunctions contribute to the development of neuropathic pain. Latexin protein expression was reduced after SNI which could be confirmed by Western Blot analysis, quantitative RT-PCR and in-situ hybridisation. The decrease of latexin was associated with an increase of the activity of carboxypeptidase A indicating that the balance between latexin and carboxypeptidase A was impaired in the spinal cord after peripheral nerve injury due to a loss of latexin expression in spinal cord neurons. This may contribute to the development of cold allodynia because normalization of neuronal latexin expression in the spinal cord by AAV-mediated latexin transduction or administration of a small molecule carboxypeptidase A inhibitor significantly reduced acetone-evoked nociceptive behavior after SNI. Our results show the usefulness of proteomics as a screening tool to identify novel mechanisms of nerve injury evoked hypernociception and suggest that carboxypeptidase A inhibition might be useful to reduce cold allodynia.
MetadatenAuthor: | Hilmar Nils Kühlein, Irmgard TegederORCiDGND, Christine Verena Möser, Hee-Young Lim, Annett Häussler, Katharina Spieth, Ingo Wilhelm Matthias Jennes, Rolf MarschalekORCiDGND, Tobias Beckhaus, Michael KarasGND, Markus Fauth, Corina Ehnert, Gerd GeisslingerORCiDGND, Ellen NiederbergerGND |
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URN: | urn:nbn:de:hebis:30-114022 |
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DOI: | https://doi.org/10.1371/journal.pone.0019270 |
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ISSN: | 1932-6203 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/21572518 |
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Parent Title (English): | PLoS One |
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Publisher: | PLoS |
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Place of publication: | Lawrence, Kan. |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2011/04/29 |
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Date of first Publication: | 2011/04/29 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2011/09/01 |
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Volume: | 6 |
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Issue: | (4): e19270 |
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Page Number: | 11 |
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First Page: | 1 |
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Last Page: | 11 |
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Note: | Copyright: © 2011 Kühlein et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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HeBIS-PPN: | 274977532 |
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Institutes: | Biochemie, Chemie und Pharmazie / Pharmazie |
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| Biowissenschaften / Biowissenschaften |
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| Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES) |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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| Sammlung Biologie / Sondersammelgebiets-Volltexte |
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Licence (German): | Creative Commons - Namensnennung 3.0 |
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