Document Detail

Proteasome inhibition suppresses Schwann cell dedifferentiation in vitro and in vivo.
MedLine Citation:
PMID:  19455715     Owner:  NLM     Status:  MEDLINE    
The ubiquitin-proteasome system (UPS), lysosomes, and autophagy are essential protein degradation systems for the regulation of a variety of cellular physiological events including the cellular response to injury. It has recently been reported that the UPS and autophagy mediate the axonal degeneration caused by traumatic insults and the retrieval of nerve growth factors. In the peripheral nerves, axonal degeneration after injury is accompanied by myelin degradation, which is tightly related to the reactive changes of Schwann cells called dedifferentiation. In this study, we examined the role of the UPS, lysosomal proteases, and autophagy in the early phase of Wallerian degeneration of injured peripheral nerves. We found that nerve injury induced an increase in the ubiquitin conjugation and lysosomal-associated membrane protein-1 expression within 1 day without any biochemical evidence for autophagy activation. Using an ex vivo explant culture of the sciatic nerve, we observed that inhibiting proteasomes or lysosomal serine proteases prevented myelin degradation, whereas this was not observed when inhibiting autophagy. Interestingly, proteasome inhibition, but not leupeptin, prevented Schwann cells from inducing dedifferentiation markers such as p75 nerve growth factor receptor and glial fibrillary acidic protein in vitro and in vivo. In addition, proteasome inhibitors induced cell cycle arrest and cellular process formation in cultured Schwann cells. Taken together, these findings indicate that the UPS plays a role in the phenotype changes of Schwann cells in response to nerve injury.
Hyun Kyoung Lee; Yoon Kyung Shin; Junyang Jung; Su-Yeong Seo; Sun-Yong Baek; Hwan Tae Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Glia     Volume:  57     ISSN:  1098-1136     ISO Abbreviation:  Glia     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-10-20     Completed Date:  2010-01-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8806785     Medline TA:  Glia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1825-34     Citation Subset:  IM    
Department of Physiology, Medical Science Research Institute, College of Medicine, Dong-A University, Seo-Gu, Busan, South Korea.
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MeSH Terms
Autophagy / drug effects,  physiology
Blotting, Western
Cell Cycle / drug effects
Cell Dedifferentiation / drug effects*
Cell Proliferation / drug effects
Cells, Cultured
Cysteine Proteinase Inhibitors / pharmacology
Fluorescent Antibody Technique
Image Processing, Computer-Assisted
Leupeptins / pharmacology
Lysosomal-Associated Membrane Protein 1 / metabolism
Lysosomes / drug effects,  metabolism
Nerve Fibers, Myelinated / drug effects,  metabolism
Proteasome Endopeptidase Complex / metabolism*
Schwann Cells / cytology,  drug effects,  metabolism*
Sciatic Nerve / cytology,  drug effects,  injuries,  metabolism*
Ubiquitination / drug effects*,  physiology
Wallerian Degeneration / metabolism
Reg. No./Substance:
0/Cysteine Proteinase Inhibitors; 0/Leupeptins; 0/Lysosomal-Associated Membrane Protein 1; 133407-82-6/benzyloxycarbonylleucyl-leucyl-leucine aldehyde; EC Endopeptidase Complex

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

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