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Oxidative Damage to Axonal Cytoskeletal Proteins

Published online by Cambridge University Press:  02 July 2020

G. Perry ,
D. A. Zelasko ,
L. M. Sayre  and
M. A. Smith
G. Perry
Affiliation:
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH, 44106
D. A. Zelasko
Affiliation:
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH, 44106
L. M. Sayre
Affiliation:
Department of Chemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH44106
M. A. Smith
Affiliation:
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH, 44106
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Extract

Proteins of the axonal cytoskeleton, particularly neurofilament and microtubule-associated protein τ, should be particularly sensitive to the effects of oxidative modification due to their high content of lysine, an amino acid that is particularly susceptible to direct oxidization as well as adduction by carbonyls produced from lipid and sugar oxidation. To understand the susceptibility of the cytoskeleton to oxidative modification and whether such modification is related to the physiological function of the cytoskeleton, we undertook a cytological analysis of motor neurons isolated from mouse spinal cord. These neurons contain an abundant axonal cytoskeleton that can be readily analyzed distinct from the cell body. Immunocytochemistry, using antibodies against protein-adducts of the highly reactive lipid peroxidation product, hydroxynonenal (HNE), representing Michael addition or pyrrole formation, revealed that HNE-immunoreactive adducts are found in all axons. This in situ distribution of HNE-adducts is consistent with immunoblots prepared from axons which show selective HNE modification of neurofilament heavy subunit (NFH) but not of other cytoskeletal proteins.

Type
Application of Novel Microscopic Approaches To Cellular Damage and Response
Information
Microscopy and Microanalysis , Volume 3 , Issue S2: Proceedings: Microscopy & Microanalysis '97, Microscopy Society of America 55th Annual Meeting, Microbeam Analysis Society 31st Annual Meeting, Histochemical Society 48th Annual Meeting, Cleveland, Ohio, August 10-14, 1997 , August 1997 , pp. 43 - 44
Copyright
Copyright © Microscopy Society of America 1997

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References

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5. This work was supported by the National Institutes of Health (AG09287 and NS22688) and the American Health Assistance Foundation. DAZ is a Ruth Salta Student Research Fellow.Google Scholar