Aggregation of alpha-synuclein induced by the Cu,Zn-superoxide dismutase and hydrogen peroxide system
- PMID: 11958955
- DOI: 10.1016/s0891-5849(02)00741-4
Aggregation of alpha-synuclein induced by the Cu,Zn-superoxide dismutase and hydrogen peroxide system
Abstract
Alpha-synuclein is a major component of the abnormal protein aggregation in Lewy bodies of Parkinson's disease (PD) and senile plaques of Alzheimer's disease (AD). Previous studies have shown that the aggregation of alpha-synuclein was induced by copper (II) and H(2)O(2) system. Since copper ions could be released from oxidatively damaged Cu,Zn-superoxide dismutase (SOD), we investigated the role of Cu,Zn-SOD in the aggregation of alpha-synuclein. When alpha-synuclein was incubated with both Cu,Zn-SOD and H(2)O(2), alpha-synuclein was induced to be aggregated. This process was inhibited by radical scavengers and spin trapping agents such as 5,5'-dimethyl 1-pyrolline N-oxide and tert-butyl-alpha-phenylnitrone. Copper chelators, diethyldithiocarbamate and penicillamine, also inhibited the Cu,Zn-SOD/H(2)O(2) system-induced alpha-synuclein aggregation. These results suggest that the aggregation of alpha-synuclein is mediated by the Cu,Zn-SOD/H(2)O(2) system via the generation of hydroxyl radical by the free radical-generating function of the enzyme. The Cu,Zn-SOD/H(2)O(2)-induced alpha-synuclein aggregates displayed strong thioflavin-S reactivity, reminiscent of amyloid. These results suggest that the Cu,Zn-SOD/H(2)O(2) system might be related to abnormal aggregation of alpha-synuclein, which may be involved in the pathogenesis of PD and related disorders.
Similar articles
-
The ceruloplasmin and hydrogen peroxide system induces alpha-synuclein aggregation in vitro.Biochimie. 2002 Jul;84(7):625-31. doi: 10.1016/s0300-9084(02)01435-9. Biochimie. 2002. PMID: 12453634
-
Enhanced oligomerization of the alpha-synuclein mutant by the Cu,Zn-superoxide dismutase and hydrogen peroxide system.Mol Cells. 2003 Feb 28;15(1):87-93. Mol Cells. 2003. PMID: 12661766
-
Formation of hydrogen peroxide and hydroxyl radicals from A(beta) and alpha-synuclein as a possible mechanism of cell death in Alzheimer's disease and Parkinson's disease.Free Radic Biol Med. 2002 Jun 1;32(11):1076-83. doi: 10.1016/s0891-5849(02)00801-8. Free Radic Biol Med. 2002. PMID: 12031892 Review.
-
Hydroxyl radical production by H2O2 plus Cu,Zn-superoxide dismutase reflects the activity of free copper released from the oxidatively damaged enzyme.J Biol Chem. 1992 Dec 15;267(35):25371-7. J Biol Chem. 1992. PMID: 1334093
-
Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer's and Parkinson's diseases.Neuromolecular Med. 2003;4(1-2):21-36. doi: 10.1385/NMM:4:1-2:21. Neuromolecular Med. 2003. PMID: 14528050 Review.
Cited by
-
Increased sulfiredoxin-1 levels as compensatory mechanism against reactive oxygen species in women with gestational diabetes mellitus.Turk J Obstet Gynecol. 2021 Dec 24;18(4):267-271. doi: 10.4274/tjod.galenos.2021.26053. Turk J Obstet Gynecol. 2021. PMID: 34955004 Free PMC article.
-
Bicarbonate enhances alpha-synuclein oligomerization and nitration: intermediacy of carbonate radical anion and nitrogen dioxide radical.Biochem J. 2004 Mar 1;378(Pt 2):435-47. doi: 10.1042/BJ20031466. Biochem J. 2004. PMID: 14640973 Free PMC article.
-
Interaction between Neuromelanin and Alpha-Synuclein in Parkinson's Disease.Biomolecules. 2015 Jun 5;5(2):1122-42. doi: 10.3390/biom5021122. Biomolecules. 2015. PMID: 26057626 Free PMC article. Review.
-
Redox reactions of the α-synuclein-Cu(2+) complex and their effects on neuronal cell viability.Biochemistry. 2010 Sep 21;49(37):8134-42. doi: 10.1021/bi1010909. Biochemistry. 2010. PMID: 20701279 Free PMC article.
-
Neuroprotective effects of Shende'an tablet in the Parkinson's disease model.Chin Med. 2021 Feb 6;16(1):18. doi: 10.1186/s13020-021-00429-y. Chin Med. 2021. PMID: 33549148 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous
