Implications for oxidative stress and astrocytes following 26S proteasomal depletion in mouse forebrain neurones

ELKHARAZ, J., UGUN-KLUSEK, A., CONSTANTIN-TEODOSIU, D., LAWLER, K., MAYER, R.J., BILLETT, E., LOWE, J. and BEDFORD, L., 2013. Implications for oxidative stress and astrocytes following 26S proteasomal depletion in mouse forebrain neurones. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1832 (12), pp. 1930-1938. ISSN 0925-4439

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Abstract

Neurodegenerative diseases are characterized by progressive degeneration of selective neurones in the nervous system, but the underlying mechanisms involved in neuroprotection and neurodegeneration remain unclear. Dysfunction of the ubiquitin proteasome system is one of the proposed hypotheses for the cause and progression of neuronal loss. We have performed quantitative two-dimensional fluorescence difference in-gel electrophoresis combined with peptide mass fingerprinting to reveal proteome changes associated with neurodegeneration following 26S proteasomal depletion in mouse forebrain neurones. Differentially expressed proteins were validated by Western blotting, biochemical assays and immunohistochemistry. Of significance was increased expression of the antioxidant enzyme peroxiredoxin 6 (PRDX6) in astrocytes, associated with oxidative stress. Interestingly, PRDX6 is a bifunctional enzyme with antioxidant peroxidase and phospholipase A2 (PLA2) activities. The PLA2 activity of PRDX6 was also increased following 26S proteasomal depletion and may be involved in neuroprotective or neurodegenerative mechanisms. This is the first in vivo report of oxidative stress caused directly by neuronal proteasome dysfunction in the mammalian brain. The results contribute to understanding neuronal–glial interactions in disease pathogenesis, provide an in vivo link between prominent disease hypotheses and importantly, are of relevance to a heterogeneous spectrum of neurodegenerative diseases.

Item Type: Journal article
Publication Title: Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease
Creators: Elkharaz, J., Ugun-Klusek, A., Constantin-Teodosiu, D., Lawler, K., Mayer, R.J., Billett, E., Lowe, J. and Bedford, L.
Publisher: Elsevier
Date: 2013
Volume: 1832
Number: 12
ISSN: 0925-4439
Identifiers:
NumberType
10.1016/j.bbadis.2013.07.002DOI
Rights: Copyright © 2013 Elsevier B.V.
Divisions: Schools > School of Science and Technology
Depositing User: EPrints Services
Date Added: 09 Oct 2015 10:02
Last Modified: 09 Jun 2017 13:17
URI: http://irep.ntu.ac.uk/id/eprint/6597

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