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Mitochondrial associated metabolic proteins are selectively oxidized in A30P alpha-synuclein transgenic mice--a model of familial Parkinson's disease.
Neurobiol Dis. 2005 Apr; 18(3):492-8.ND

Abstract

Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra compacta. alpha-Synuclein is strongly implicated in the pathophysiology of PD because aggregated alpha-synuclein accumulates in the brains of subjects with PD, mutations in alpha-synuclein cause familial PD, and overexpressing mutant human alpha-synuclein (A30P or A53T) causes degenerative disease in mice or drosophila. The pathophysiology of PD is poorly understood, but increasing evidence implicates mitochondrial dysfunction and oxidative stress. To understand how mutations in alpha-synuclein contribute to the pathophysiology of PD, we undertook a proteomic analysis of transgenic mice overexpressing A30P alpha-synuclein to investigate which proteins are oxidized. We observed more than twofold selective increases in specific carbonyl levels of three metabolic proteins in brains of symptomatic A30P alpha-synuclein mice: carbonic anhydrase 2 (Car2), alpha-enolase (Eno1), and lactate dehydrogenase 2 (Ldh2). Analysis of the activities of these proteins demonstrates decreased functions of these oxidatively modified proteins in brains from the A30P compared to control mice. Our findings suggest that proteins associated with impaired energy metabolism and mitochondria are particularly prone to oxidative stress associated with A30P-mutant alpha-synuclein.

Authors+Show Affiliations

Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15755676

Citation

Poon, H Fai, et al. "Mitochondrial Associated Metabolic Proteins Are Selectively Oxidized in A30P Alpha-synuclein Transgenic Mice--a Model of Familial Parkinson's Disease." Neurobiology of Disease, vol. 18, no. 3, 2005, pp. 492-8.
Poon HF, Frasier M, Shreve N, et al. Mitochondrial associated metabolic proteins are selectively oxidized in A30P alpha-synuclein transgenic mice--a model of familial Parkinson's disease. Neurobiol Dis. 2005;18(3):492-8.
Poon, H. F., Frasier, M., Shreve, N., Calabrese, V., Wolozin, B., & Butterfield, D. A. (2005). Mitochondrial associated metabolic proteins are selectively oxidized in A30P alpha-synuclein transgenic mice--a model of familial Parkinson's disease. Neurobiology of Disease, 18(3), 492-8.
Poon HF, et al. Mitochondrial Associated Metabolic Proteins Are Selectively Oxidized in A30P Alpha-synuclein Transgenic Mice--a Model of Familial Parkinson's Disease. Neurobiol Dis. 2005;18(3):492-8. PubMed PMID: 15755676.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitochondrial associated metabolic proteins are selectively oxidized in A30P alpha-synuclein transgenic mice--a model of familial Parkinson's disease. AU - Poon,H Fai, AU - Frasier,Mark, AU - Shreve,Nathan, AU - Calabrese,Vittorio, AU - Wolozin,Benjamin, AU - Butterfield,D Allan, PY - 2004/07/28/received PY - 2004/12/16/revised PY - 2004/12/22/accepted PY - 2005/3/10/pubmed PY - 2005/5/18/medline PY - 2005/3/10/entrez SP - 492 EP - 8 JF - Neurobiology of disease JO - Neurobiol Dis VL - 18 IS - 3 N2 - Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra compacta. alpha-Synuclein is strongly implicated in the pathophysiology of PD because aggregated alpha-synuclein accumulates in the brains of subjects with PD, mutations in alpha-synuclein cause familial PD, and overexpressing mutant human alpha-synuclein (A30P or A53T) causes degenerative disease in mice or drosophila. The pathophysiology of PD is poorly understood, but increasing evidence implicates mitochondrial dysfunction and oxidative stress. To understand how mutations in alpha-synuclein contribute to the pathophysiology of PD, we undertook a proteomic analysis of transgenic mice overexpressing A30P alpha-synuclein to investigate which proteins are oxidized. We observed more than twofold selective increases in specific carbonyl levels of three metabolic proteins in brains of symptomatic A30P alpha-synuclein mice: carbonic anhydrase 2 (Car2), alpha-enolase (Eno1), and lactate dehydrogenase 2 (Ldh2). Analysis of the activities of these proteins demonstrates decreased functions of these oxidatively modified proteins in brains from the A30P compared to control mice. Our findings suggest that proteins associated with impaired energy metabolism and mitochondria are particularly prone to oxidative stress associated with A30P-mutant alpha-synuclein. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/15755676/Mitochondrial_associated_metabolic_proteins_are_selectively_oxidized_in_A30P_alpha_synuclein_transgenic_mice__a_model_of_familial_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(04)00320-1 DB - PRIME DP - Unbound Medicine ER -