Coupling of Dopamine Oxidation (Monoamine Oxidase Activity) to Glutathione Oxidation Via the Generation of Hydrogen Peroxide in Rat Brain Homogenates

Maker, Howard S.; Weiss, Carlos O.; Silides, Demetra J.; Cohen, Gerald

doi:10.1111/j.1471-4159.1981.tb01631.x

Cited by 240 publications

(106 citation statements)

References 20 publications

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“…Although we currently have no available methods for measuring cytoplasmic dopamine in neurons, dopamine-dependent oxidative stress can be measured indirectly. In the cytosol, dopamine can auto-oxidize into dopamine-quinone species, superoxide radicals, and hydrogen peroxide (Graham, 1978) or can be enzymatically deaminated by monoamine oxidase into the nontoxic metabolite 3,4-dihydroxyphenylacetic acid and hydrogen peroxide (Maker et al, 1981). Superoxide and hydrogen peroxide can be measured by various methods.…”

Section: Blockade Of Fe 2؉ /Meth-induced Oxidative Stress By Cep1347mentioning

confidence: 99%

“…Nigral dopaminergic neurons are under continuous oxidative stress because of the unstable nature of their neurotransmitter dopamine (Graham, 1978;Maker et al, 1981), the adverse effects of which are further enhanced by high concentrations of iron in the substantia nigra (SN) (for review, see Zecca et al, 2004). Experimental studies using methamphetamine (METH) suggest that abnormal accumulation of cytoplasmic dopamine could play an important role in disease pathogenesis by inducing oxidative stress (for review, see .…”

Section: Introductionmentioning

confidence: 99%

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Progressive Degeneration of Human Mesencephalic Neuron-Derived Cells Triggered by Dopamine-Dependent Oxidative Stress Is Dependent on the Mixed-Lineage Kinase Pathway

Lotharius

Falsig²,

Beek³

et al. 2005

J. Neurosci.

232

240

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Models of Parkinson's disease (PD) based on selective neuronal death have been used to study pathogenic mechanisms underlying nigral cell death and in some instances to develop symptomatic therapies. For validation of putative neuroprotectants, a model is desirable in which the events leading to neurodegeneration replicate those occurring in the disease. We developed a human in vitro model of PD based on the assumption that dysregulated cytoplasmic dopamine levels trigger cell loss in this disorder. Differentiated human mesencephalic neuron-derived cells were exposed to methamphetamine (METH) to promote cytoplasmic dopamine accumulation. In the presence of elevated iron concentrations, as observed in PD, increased cytosolic dopamine led to oxidative stress, c-Jun N-terminal kinase (JNK) pathway activation, neurite degeneration, and eventually apoptosis. We examined the role of the mixed-lineage kinases (MLKs) in this complex degenerative cascade by using the potent inhibitor 3,9 -bis[(ethylthio)methyl]-K-252a (CEP1347). Inhibition of MLKs not only prevented FeCl2ϩ /METH-induced JNK activation and apoptosis but also early events such as neurite degeneration and oxidative stress. This broad neuroprotective action of CEP1347 was associated with increased expression of an oxidative stress-response modulator, activating transcription factor 4. As a functional consequence, transcription of the cystine/glutamate and glycine transporters, cellular cystine uptake and intracellular levels of the redox buffer glutathione were augmented. In conclusion, this new human model of parkinsonian neurodegeneration has the potential to yield new insights into neurorestorative therapeutics and suggests that enhancement of cytoprotective mechanisms, in addition to blockade of apoptosis, may be essential for disease modulation.

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Section: Blockade Of Fe 2؉ /Meth-induced Oxidative Stress By Cep1347mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Progressive Degeneration of Human Mesencephalic Neuron-Derived Cells Triggered by Dopamine-Dependent Oxidative Stress Is Dependent on the Mixed-Lineage Kinase Pathway

Lotharius

Falsig²,

Beek³

et al. 2005

J. Neurosci.

232

240

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“…Low levels of D2R may cause an increase of dopamine release from catecholaminergic neurons, which may lead to exceeding dopamine levels in both extracellular and intracellular environments of post-synaptic neurons (Lotharius andBrundin 2002, Jorg et al 2014). Dopamine is very reactive under physiologic pH, giving rise to semi-quinones that may react with thiol groups in protein and affect its structure and function (Graham 1978, Maker et al 1981, Lotharius and Brundin 2002. In fact, increased concentration of oxidized protein thiol groups was observed in that experimental model.…”

Section: Molecular Evidences Of Vitamin A-related Neurotoxicitymentioning

confidence: 95%

The neurotoxic effects of vitamin A and retinoids

Oliveira

2015

An. Acad. Bras. Ciênc.

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Vitamin A (retinol) and its congeners -the retinoids -participate in a panoply of biological events, as for instance cell differentiation, proliferation, survival, and death, necessary to maintain tissue homeostasis. Furthermore, such molecules may be applied as therapeutic agents in the case of some diseases, including dermatological disturbances, immunodeficiency, and cancer (mainly leukemia). In spite of this, there is a growing body of evidences showing that vitamin A doses exceeding the nutritional requirements may lead to negative consequences, including bioenergetics state dysfunction, redox impairment, altered cellular signaling, and cell death or proliferation, depending on the cell type. Neurotoxicity has long been demonstrated as a possible side effect of inadvertent consumption, or even under medical recommendation of vitamin A and retinoids at moderate to high doses. However, the exact mechanism by which such molecules exert a neurotoxic role is not clear yet. In this review, recent data are discussed regarding the molecular findings associated with the vitamin A-related neurotoxicity.

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“…Dopamine can react with hydroxyl radicals to form the dopaminergic neurotoxin 6-hydroxydopamine, which generates free radicals during its spontaneous rapid autooxidation (47). Furthermore, the enzymatic oxidation of dopamine by monoamine oxidase results in the formation of hydrogen peroxide, a hydroxyl radical precursor (48).…”

mentioning

confidence: 99%

Intrauterine Growth Restriction Induces Up-Regulation of Cerebral Aromatic Amino Acid Decarboxylase Activity in Newborn Piglets: [18F]Fluorodopa Positron Emission Tomographic Study

et al. 2001

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There is evidence that intrauterine growth restriction (IUGR) is associated with altered dopaminergic function in the immature brain. However, the relevant enzyme activities have not been measured in the living neonatal brain together with brain oxidative metabolism. Therefore, fluorine-18-labeled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) was used together with positron emission tomography to estimate the activity of the aromatic amino acid decarboxylase in the brain of 10 newborn IUGR piglets (2 to 5 d old; body weight, 908 Ϯ 109 g) and in 10 normal-weight (3 to 5 d old; body weight, 2142 Ϯ 373 g) newborn piglets. The regional transport of FDOPA to the brain and the clearance rate of labeled metabolites from brain tissue were broadly similar in the two groups. However, the regional rate constant for back flux from the brain was markedly increased in IUGR piglets for striatum (72%) and frontal cortex (83%) (p Ͻ 0.05). Furthermore, the rate constant for conversion of FDOPA to fluorodopamine was markedly increased (between 48% in cerebellum and 91% in mesencephalon, p Ͻ 0.05) in all brain regions of IUGR piglets studied. Thus, it is suggested that IUGR induces an up-regulation of aromatic amino acid decarboxylase activity that is not related to alterations in brain oxidative metabolism. An inadequate nutritional supply due to uteroplacental insufficiency or restricted maternal protein intake late in gestation is largely responsible for asymmetrical IUGR (1). Reduced fetal growth can be viewed as a compensation for the reduced supply as long as fetal demand is not critically restricted, leading to decompensation with asphyxia and even death (2). The compromised nutritional state has adverse effects on fetal physiology and metabolism including changes of hormonal homeostasis (3), which are thought to be associated with postnatal growth failure and a greater propensity to develop cardiovascular metabolic disease or behavioral abnormalities later in life (4). Therefore, the period of fetal adaptation, characterized by reduced growth due to restricted glucose and amino acid availability but largely compensated placental respiratory function (5), reflects a functional state that may lead to both acceleration or delay in organ maturation (6, 7).The importance of the intrauterine environment for fetal brain development has been stressed by studies showing persistent behavioral abnormalities in prenatally stressed animals (8). Rats exposed to noise and light stress during the last trimester of pregnancy produce offspring with altered locomo- ABSTRACT474

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Coupling of Dopamine Oxidation (Monoamine Oxidase Activity) to Glutathione Oxidation Via the Generation of Hydrogen Peroxide in Rat Brain Homogenates

Cited by 240 publications

References 20 publications

Progressive Degeneration of Human Mesencephalic Neuron-Derived Cells Triggered by Dopamine-Dependent Oxidative Stress Is Dependent on the Mixed-Lineage Kinase Pathway

Progressive Degeneration of Human Mesencephalic Neuron-Derived Cells Triggered by Dopamine-Dependent Oxidative Stress Is Dependent on the Mixed-Lineage Kinase Pathway

The neurotoxic effects of vitamin A and retinoids

Intrauterine Growth Restriction Induces Up-Regulation of Cerebral Aromatic Amino Acid Decarboxylase Activity in Newborn Piglets: [18F]Fluorodopa Positron Emission Tomographic Study

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