Please note that eDoc will be permanently shut down in the first quarter of 2021!      Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für neurologische Forschung     Collection: Emeritus-Collection Prof. Hossmann     Display Documents



ID: 13144.0, MPI für neurologische Forschung / Emeritus-Collection Prof. Hossmann
Down-regulation of parkin protein in transient focal cerebral ischemia: A link between stroke and degenerative disease?
Authors:Mengesdorf, Thorsten; Jensen, P. H.; Mies, Günter; Aufenberg, Christoph; Paschen, Wulf
Language:English
Date of Publication (YYYY-MM-DD):2002-11-12
Title of Journal:Proceedings of the National Academy of Sciences of the United States of America
Journal Abbrev.:Proc. Natl. Acad. Sci. U. S. A.
Volume:99
Issue / Number:23
Start Page:15042
End Page:15047
Copyright:Copyright by the National Academy of Sciences of the United States of America, all rights reserved
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Ubiquitylated protein aggregates are characteristic features of neurodegenerative disorders that are also found in acute pathological states of the brain such as stroke. Many of the proteins connected to neurodegenerative diseases play a role in the ubiquitin-proteasomal pathway. Mutation of one of these proteins, the E3 ubiquitin ligase parkin, is the cause of autosomal recessive juvenile Parkinson's disease. Here we show that transient focal cerebral ischemia of 1-h duration induces marked depletion of parkin protein levels, to 60%, 36%, 33%, and 25% of controls after 1, 3, 6, and 24 h of reperfusion, but that ischemia does not cause lower protein levels of E2 ubiquitin-conjugating enzymes Ubc6, Ubc7, or Ubc9. After 3 h of reperfusion, when parkin protein levels were already reduced to <40% of control, ATP levels were almost completely recovered from ischemia and we did not observe DNA fragmentation, suggesting that parkin depletion preceded development of neuronal cell death. Up-regulation of the expression of parkin has been shown to protect cells from injury induced by endoplasmic reticulum (ER) dysfunction, and this form of cellular stress is also triggered by transient cerebral ischemia. However, in contrast to observations in neuroblastoma cells, we saw no up-regulation of parkin expression in primary neuronal cell cultures after induction of ER dysfunction. Our data thus suggest that ischemia-induced depletion of parkin protein may contribute to the pathological process resulting in cell injury by increasing the sensitivity of neurons to ER dysfunction and the aggregation of ubiquitylated proteins during the reperfusion period.
Comment of the Author/Creator:Date: 2002, NOV 12
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für neurologische Forschung/Experimentelle Neurologie - Abt. Prof. Hossmann
External Affiliations:Max Planck Inst Neurol Res, Dept Expt Neurol, Gleueler Str 50,; D-50931 Cologne, Germany; Max Planck Inst Neurol Res, Dept Expt Neurol, D-50931 Cologne, Germany; Aarhus Univ, Dept Med Biochem, DK-8000 Aarhus, Denmark
Identifiers:ISI:000179224800078 [ID No:1]
ISSN:0027-8424 [ID No:2]
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.