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A variety of in vitro and in vivo studies demonstrate that dopamine is a toxic molecule that may contribute to neurodegenerative disorders such as Parkinson's disease and ischemia-induced striatal damage. While much attention has focused on the fact that the metabolism of dopamine produces reactive oxygen species (peroxide, superoxide, and hydroxyl(More)
Dopamine has been implicated as a potential mediating factor in a variety of neurodegenerative disorders. Dopamine can be oxidized to form a reactive dopamine quinone that can covalently modify cellular macromolecules including protein and DNA. This oxidation can be enhanced through various enzymes including tyrosinase and/or prostaglandin H synthase. One(More)
Dopamine acts, under appropriate conditions, as a selective neurotoxin. This toxicity is attributed to the autoxidation of the neurotransmitter into a reactive quinone that covalently modifies cellular macromolecules (i.e. proteins and nucleic acids). The oxidation of the catecholamine to a quinone is greatly accelerated by the enzyme tyrosinase. There is(More)
Dopamine (DA), while an essential neurotransmitter, is also a known neurotoxin that potentially plays an etiologic role in several neurodegenerative diseases. DA metabolism and oxidation readily produce reactive oxygen species (ROS) and DA can also be oxidized to a reactive quinone via spontaneous, enzyme-catalyzed or metal-enhanced reactions. A number of(More)
Manganese (Mn) is an essential metal that, at excessive levels in the brain, produces extrapyramidal symptoms similar to those in patients with Parkinson's disease (PD). In the present study, Mn toxicity was characterized in a human neuroblastoma (SK-N-SH) cell line and in a mouse catecholaminergic (CATH.a) cell line. Mn was demonstrated to be more toxic in(More)
Dopamine (DA) metabolism and oxidation produce both reactive oxygen species (ROS) and reactive quinones. These chemical species are implicated in dopamine neurotoxicity and neurodegeneration. In the present studies, human neuroblastoma (SK-N-SH) cells were exposed to toxic concentrations of dopamine (333 microM) in order to investigate molecular pathways(More)
Dopamine-induced DNA damage was studied in vitro in the presence of the enzyme tyrosinase. Dopamine auto-oxidizes to form dopamine quinone, a reactive molecule which spontaneously decomposes to form additional reactive species that can modify cellular macromolecules. The conversion of dopamine to reactive dopamine quinone is accelerated by the enzyme(More)
Tryptophan hydroxylase (TPH) is the initial and rate-limiting enzyme in serotonin biosynthesis. The enzyme activity is dependent on molecular oxygen, a tetrahydropterin cosubstrate, and ferrous iron. The present study demonstrates that TPH is inhibited by a novel compound, p-ethynylphenylalanine (pEPA), produced by the Heck reaction of(More)
Cultured rat mesencephalic neurons were used to assess the effects of gamma-aminobutyric acid (GABA) transport blockers on toxicity caused by malonate, a reversible, competitive inhibitor of succinate dehydrogenase. Previous studies utilizing an ex vivo chick retinal preparation have shown that GABA release and cell swelling are early consequences of acute(More)
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