Neuronal ceroid lipofuscinosis type 6 and its sheep model (OCL6) are lysosomal storage disorders caused by mutations in the CLN6 gene product of unknown function. It has been proposed that mitochondrial dysfunction, including defects in mitochondrial protein degradation, organelle enlargement and functional changes in oxidative phosphorylation, may contribute to the disease pathology. To further explore the disease mechanisms underlying CLN6, protein expression was compared between normal and affected tissues. Using two-dimensional electrophoretic separation of proteins, MS and immunoblotting, MnSOD (manganese-dependent superoxide dismutase) was found to be significantly and specifically increased in fibroblasts and brain extracts of both human and sheep affected with CLN6. Both the activity and expression of MnSOD mRNA were enhanced in affected fibroblasts. Confocal fluorescence microscopy and immunohistochemical studies revealed the presence of MnSOD in mitochondria of CLN6 fibroblasts and in CLN6 brain sections within both neurons and hypertrophic astrocytes. These data suggest that oxidative stress and/or the production of pro-inflammatory cytokines are characteristic features of human and sheep CLN6, resulting in elevated expression of MnSOD, which may be important for diagnostic purposes.
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December 2003
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Research Article|
December 01 2003
Enhanced expression of manganese-dependent superoxide dismutase in human and sheep CLN6 tissues Available to Purchase
Claudia HEINE;
Claudia HEINE
*Children's Hospital, University of Hamburg, 20246 Hamburg, Germany
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Jaana TYYNELÄ;
Jaana TYYNELÄ
†Institute of Biomedicine/Biochemistry, University of Helsinki, 00014 Helsinki, Finland
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Jonathan D. COOPER;
Jonathan D. COOPER
‡Institute of Psychiatry, King's College London, London SE5 8AF, U.K.
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David N. PALMER;
David N. PALMER
§Animal and Food Sciences Division, Lincoln University, Canterbury, New Zealand
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Milan ELLEDER;
Milan ELLEDER
‖Institute of Inherited Metabolic Disorders, Charles University Prague, 121 11 Prague 2, Czech Republic
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Alfried KOHLSCHÜTTER;
Alfried KOHLSCHÜTTER
*Children's Hospital, University of Hamburg, 20246 Hamburg, Germany
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Thomas BRAULKE
Thomas BRAULKE
1
*Children's Hospital, University of Hamburg, 20246 Hamburg, Germany
1To whom correspondence should be addressed (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
April 22 2003
Revision Received:
August 28 2003
Accepted:
August 29 2003
Accepted Manuscript online:
August 29 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 376 (2): 369–376.
Article history
Received:
April 22 2003
Revision Received:
August 28 2003
Accepted:
August 29 2003
Accepted Manuscript online:
August 29 2003
Citation
Claudia HEINE, Jaana TYYNELÄ, Jonathan D. COOPER, David N. PALMER, Milan ELLEDER, Alfried KOHLSCHÜTTER, Thomas BRAULKE; Enhanced expression of manganese-dependent superoxide dismutase in human and sheep CLN6 tissues. Biochem J 1 December 2003; 376 (2): 369–376. doi: https://doi.org/10.1042/bj20030598
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