Abstract
Structural and functional alterations of alpha-synuclein is a presumed culprit in the demise of dopaminergic neurons in Parkinson's disease (PD). Alpha-synuclein mutations are found in familial but not in sporadic PD, raising the hypothesis that effects similar to those of familial PD-linked alpha-synuclein mutations may be achieved by oxidative post-translational modifications. Here, we show that wild-type alpha-synuclein is a selective target for nitration following peroxynitrite exposure of stably transfected HEK293 cells. Nitration of alpha-synuclein also occurs in the mouse striatum and ventral midbrain following administration of the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Conversely, beta-synuclein and synaptophysin were not nitrated in MPTP-intoxicated mice. Our data demonstrate that alpha-synuclein is a target for tyrosine nitration, which, by disrupting its biophysical properties, may be relevant to the putative role of alpha-synuclein in the neurodegeneration associated with MPTP toxicity and with PD.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine*
-
Animals
-
Cell Line
-
Corpus Striatum / chemistry
-
Corpus Striatum / drug effects
-
Corpus Striatum / metabolism
-
Disease Models, Animal
-
Humans
-
Kidney / chemistry
-
Kidney / cytology
-
Kidney / drug effects
-
Kidney / metabolism
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Nerve Tissue Proteins / chemistry
-
Nerve Tissue Proteins / genetics
-
Nerve Tissue Proteins / metabolism*
-
Oxidation-Reduction / drug effects
-
Parkinsonian Disorders / chemically induced
-
Parkinsonian Disorders / metabolism*
-
Peroxynitrous Acid / pharmacology
-
Precipitin Tests
-
Protein Processing, Post-Translational / physiology*
-
Synaptophysin / analysis
-
Synaptophysin / metabolism
-
Synucleins
-
Transfection
-
Tyrosine / chemistry
-
Tyrosine / drug effects
-
Tyrosine / metabolism
-
alpha-Synuclein
-
beta-Synuclein
Substances
-
Nerve Tissue Proteins
-
SNCA protein, human
-
SNCB protein, human
-
Snca protein, mouse
-
Sncb protein, mouse
-
Synaptophysin
-
Synucleins
-
alpha-Synuclein
-
beta-Synuclein
-
Peroxynitrous Acid
-
Tyrosine
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine