Increased oxidative stresses are implicated in the pathogenesis of Parkinson's disease, and dopaminergic neurons may be intrinsically susceptible to oxidative damage. However, the selective presence of tetrahydrobiopterin (BH(4)) makes dopaminergic neurons more resistant to oxidative stress caused by glutathione depletion. To further investigate the mechanisms of BH(4) protection, we examined the effects of BH(4) on superoxide levels in individual living mesencephalic neurons. Dopaminergic neurons have intrinsically lower levels of superoxide than nondopaminergic neurons. In addition, inhibiting BH(4) synthesis increased superoxide in dopaminergic neurons, while BH(4) supplementation decreased superoxide in nondopaminergic cells. BH(4) is also a cofactor in catecholamine and NO production. In order to exclude the possibility that the antioxidant effects of BH(4) are mediated by dopamine and NO, we used fibroblasts in which neither catecholamine nor NO production occurs. In fibroblasts, BH(4) decreased baseline reactive oxygen species, and attenuated reactive oxygen species increase by rotenone and antimycin A. Physiologic concentrations of BH(4) directly scavenged superoxide generated by potassium superoxide in vitro. We hypoth...Continue Reading
Mitochondrial function in Parkinson's disease. The Royal Kings and Queens Parkinson's Disease Research Group
Reduction of brain glutathione by L-buthionine sulfoximine potentiates the dopamine-depleting action of 6-hydroxydopamine in rat striatum
Further studies on the formation of oxygen radicals by potassium superoxide in aqueous medium for biochemical investigations
Inhibition of monocyte luminol-dependent chemiluminescence by tetrahydrobiopterin, and the free radical oxidation of tetrahydrobiopterin, dihydrobiopterin and dihydroneopterin
Tetrahydrobiopterin in striatum: localization in dopamine nerve terminals and role in catecholamine synthesis
Antioxidative activity of 5,6,7,8-tetrahydrobiopterin and its inhibitory effect on paraquat-induced cell toxicity in cultured rat hepatocytes
Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia
Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease
Different mechanisms of glutamate-induced neuronal death between dopaminergic and non-dopaminergic neurons in rat mesencephalic culture
Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase
Tetrahydrobiopterin biosynthesis in the rat brain: heterogeneity of GTP cyclohydrolase I mRNA expression in monoamine-containing neurons
Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants
Generation of reactive oxygen species by tyrosine hydroxylase: a possible contribution to the degeneration of dopaminergic neurons?
Quantitative measurement of superoxide generation using the spin trap 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide
Tetrahydrobiopterin regulates superoxide and nitric oxide generation by recombinant endothelial nitric oxide synthase
Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra
A generalised increase in protein carbonyls in the brain in Parkinson's but not incidental Lewy body disease
ADP-regulation of mitochondrial free radical production is different with complex I- or complex II-linked substrates: implications for the exercise paradox and brain hypermetabolism
Mitochondrial membrane potential and hydroethidine-monitored superoxide generation in cultured cerebellar granule cells
Association of IgM type anti-GM1 antibodies and muscle strength in chronic acquired demyelinating polyneuropathy
Influence of development and aging on brain biopterin: implications for dopa-responsive dystonia onset
Superoxide generation from endothelial nitric-oxide synthase. A Ca2+/calmodulin-dependent and tetrahydrobiopterin regulatory process.
Interaction of alpha-phenyl-N-tert-butyl nitrone and alternative electron acceptors with complex I indicates a substrate reduction site upstream from the rotenone binding site
Detection of reactive nitrogen species using 2,7-dichlorodihydrofluorescein and dihydrorhodamine 123
SIN-1-induced cytotoxicity in cultured endothelial cells involves reactive oxygen species and nitric oxide: protective effect of sepiapterin
Tetrahydrobiopterin-dependent inhibition of superoxide generation from neuronal nitric oxide synthase.
Preferential resistance of dopaminergic neurons to the toxicity of glutathione depletion is independent of cellular glutathione peroxidase and is mediated by tetrahydrobiopterin
Preferential resistance of dopaminergic neurons to glutathione depletion in a reconstituted nigrostriatal system
Alterations of tetrahydrobiopterin biosynthesis and pteridine levels in mouse tissues during growth and aging
Age-related decreases in GTP-cyclohydrolase-I immunoreactive neurons in the monkey and human substantia nigra
Loss of striatal dopaminergic fibers after intraventricular injection of tetrahydrobiopterin in rat brain
Effect of fraxetin on antioxidant defense and stress proteins in human neuroblastoma cell model of rotenone neurotoxicity. Comparative study with myricetin and N-acetylcysteine
Paraquat induces long-lasting dopamine overflow through the excitotoxic pathway in the striatum of freely moving rats
Oxidation of tetrahydrobiopterin by biological radicals and scavenging of the trihydrobiopterin radical by ascorbate
Catechin attenuates 6-hydroxydopamine (6-OHDA)-induced cell death in primary cultures of mesencephalic cells
Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein.
Cyclin-G-associated kinase modifies α-synuclein expression levels and toxicity in Parkinson's disease: results from the GenePD Study
Arsenic: signal transduction, transcription factor, and biotransformation involved in cellular response and toxicity
Characterization of transgenic Gfrp knock-in mice: implications for tetrahydrobiopterin in modulation of normal tissue radiation responses
Chronic administration of rotenone increases levels of nitric oxide and lipid peroxidation products in rat brain
Understanding the susceptibility of dopamine neurons to mitochondrial stressors in Parkinson's disease
Particular vulnerability of rat mesencephalic dopaminergic neurons to tetrahydrobiopterin: Relevance to Parkinson's disease
Standardized Hypericum perforatum reduces oxidative stress and increases gene expression of antioxidant enzymes on rotenone-exposed rats
Murine succinate semialdehyde dehydrogenase (SSADH) deficiency, a heritable disorder of GABA metabolism with epileptic phenotype
Dopamine-dependent cytotoxicity of tetrahydrobiopterin: a possible mechanism for selective neurodegeneration in Parkinson's disease
Nitrotyrosine as a marker for peroxynitrite-induced neurotoxicity: the beginning or the end of the end of dopamine neurons?
Tetrahydrobiopterin precursor sepiapterin provides protection against neurotoxicity of 1-methyl-4-phenylpyridinium in nigral slice cultures
Plasma selenium is positively related to performance in neurological tasks assessing coordination and motor speed
Low complex I content explains the low hydrogen peroxide production rate of heart mitochondria from the long-lived pigeon, Columba livia
Potential therapeutic applications of tetrahydrobiopterin: from inherited hyperphenylalaninemia to mitochondrial diseases
Glutathione depletion in nigrostriatal slice cultures: GABA loss, dopamine resistance and protection by the tetrahydrobiopterin precursor sepiapterin
Glutathione production is regulated via distinct pathways in stressed and non-stressed cortical neurons
Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling
1-Methyl-4-phenylpyridinium-induced apoptosis in cerebellar granule neurons is mediated by transferrin receptor iron-dependent depletion of tetrahydrobiopterin and neuronal nitric-oxide synthase-derived superoxide.
Overexpression of V-1 prevents nitric oxide-induced cell death: involvement of enhanced tetrahydrobiopterin biosynthesis
Distinct mechanisms of neurodegeneration induced by chronic complex I inhibition in dopaminergic and non-dopaminergic cells.
Inhibition of complex I of the electron transport chain causes O2-. -mediated mitochondrial outgrowth
Neuroprotective therapy in Parkinson's disease: current status and new directions from experimental and genetic clues
Superoxide (*O2- ) production in CA1 neurons of rat hippocampal slices exposed to graded levels of oxygen
Tetrahydrobiopterin prevents nitration of tyrosine hydroxylase by peroxynitrite and nitrogen dioxide
The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.
Amygdala and Midbrain Dopamine
The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.