Nonoxidative protein glycation is implicated in familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation |
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Authors: | N Shibata R Nagai S Miyata T Jono S Horiuchi A Hirano S Kato S Sasaki K Asayama M Kobayashi |
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Institution: | (1) Department of Pathology, Tokyo Women’s Medical University, Kawada-cho 8-1, Shinjuku-ku, Tokyo 162-8666, Japan Tel.: +81-3-33538111 ext 22233, Fax: +81-3-52697408, JP;(2) Department of Biochemistry, Kumamoto University School of Medicine, Honjo 2-2-1, Kumamoto 860-0811, Japan, JP;(3) Second Department of Internal Medicine, Kobe University School of Medicine, Kusunoki-cho 7-5-1, Chuo-ku, Kobe 650-0017, Japan, JP;(4) Division of Neuropathology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467-2490, USA, US;(5) Division of Neuropathology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Nishi-machi 86, Yonago 683-8503, Japan, JP;(6) Department of Neurology, Tokyo Women’s Medical University, Kawada-cho 8-1, Shinjuku-ku, Tokyo 162-8666, Japan, JP;(7) Department of Pediatrics, Yamanashi Medical University, Shimokato 1110, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan, JP |
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Abstract: | To assess a role for oxidative stress in the pathogenesis of amyotrophic lateral sclerosis (ALS), we analyzed the immunohistochemical
localization of 8-hydroxy-2′-deoxyguanosine (OHdG) as a nucleic acid oxidation product, acrolein-protein adduct and 4-hydroxy-2-nonenal
(HNE)-protein adduct as lipid peroxidation products, N
ɛ-carboxymethyl-lysine (CML) as a lipid peroxidation or protein glycoxidation product, pentosidine as a protein glycoxidation
product, and imidazolone and pyrraline as nonoxidative protein glycation products in the spinal cord of three familial ALS
patients with superoxide dismutase-1 (SOD1) A4V mutation, six sporadic ALS patients, and six age-matched control individuals.
The spinal cord sections of the control cases did not show any distinct immunoreactivities for these examined products. In
the familial ALS cases, intense immunoreactivities for pyrraline and CML were confined to the characteristic Lewy body-like
hyaline inclusions, and imidazolone immunoreactivity was located in the cytoplasm of the residual motor neurons. No significant
immunoreactivities for other examined products were detected in the familial ALS spinal cords. In the sporadic ALS cases,
intense immunoreactivities for pentosidine, CML and HNE-protein adduct were seen in the cytoplasm of the degenerated motor
neurons, and OHdG immunoreactivity was located in the cell nuclei of the residual neurons and glial cells. The present results
indicate that oxidative reactions are involved in the disease processes of sporadic ALS, while there is no evidence for increased
oxidative damage except for CML deposition in the familial ALS spinal cords. Furthermore, it is likely that the accumulation
of pyrraline and imidazolone supports a nonoxidative mechanism in SOD1-related motor neuron degeneration.
Received: 18 August 1999 / Revised, accepted: 17 November 1999 |
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Keywords: | Amyotrophic lateral sclerosis Imidazolone Nɛ -carboxymethyl-lysine Pyrraline Superoxide dismutase |
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