Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase

Xu, Yimei; Stokes, Alan H.; Roskoski, Robert; Vrana, Kent E.

doi:10.1002/(sici)1097-4547(19981201)54:5<691::aid-jnr14>3.0.co;2-f

Cited by 167 publications

(82 citation statements)

References 32 publications

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“…The absence of substrate nitration in tyrosinase/O 2 /NO-mediated reactions with either L-dopa or dopamine may document a significantly different method of converting o-diphenols to o-quinones than that employed by peroxidase/H 2 O 2 . This possibility highlights the importance of several recent studies documenting the presence of tyrosinase in the brain (47)(48)(49)(50)(51) and reports that enzyme activity (11,19,52) and melanogenesis are enhanced by NO modulating tyrosinase gene expression via the cGMP pathway (19,52). In our investigations we found that the amount of substrate oxidized in reactions containing both tyrosinase and NO was less than additive, suggesting enzyme inhibition.…”

Section: Figsupporting

confidence: 76%

The Effects of Nitric Oxide on the Oxidations ofl-Dopa and Dopamine Mediated by Tyrosinase and Peroxidase

Nappi

Vass

2001

Journal of Biological Chemistry

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The effects of nitric oxide (NO) on both tyrosinase/O 2 -and horseradish peroxidase/H 2 O 2 -mediated oxidations of dopamine and its o-dihydric phenol precursor L-dopa were compared with autoxidative processes and quantitatively assessed by oxidative and reductive electrochemical detection systems. In peroxidase/H 2 O 2 /NO-catalyzed reactions, significantly more substrate was oxidized than in the corresponding control incubations lacking NO. In tyrosinase/O 2 /NO-promoted reactions the total amounts of L-dopa and dopamine oxidized were significantly less than the amounts of the substrates oxidized by enzyme alone. These data indicate that the activity of the heme protein peroxidase was enhanced by NO, whereas tyrosinase, a copper-containing monoxygenase, was inhibited. The NO-mediated reduction of tyrosinase/O 2 activity may be attributed to the formation of an inhibitory copper⅐nitrosyl complex. An oxidized nitrodopamine derivative, considered to be either the quinone or semiquinone of 6-nitrosodopamine, was generated in peroxidase/H 2 O 2 /NO-mediated reactions with dopamine along with two oxidized melanin precursors, dopamine quinone and dopaminechrome. No corresponding nitroso compound was formed in reactions involving L-dopa or in any of the tyrosinase-mediated reactions. The formation of such a noncyclized nitrosodopamine represents an important alternative pathway in catecholamine metabolism, one that by-passes the formation of cytoprotective indole precursors of melanin. The results of this investigation suggest that cellular integrity and function can be adversely affected by NO-promoted oxidations of dopamine and other catechols, reactions that not only accelerate their conversion to reactive quinones but also form potentially cytotoxic noncyclized nitroso derivatives. Reduced levels of dopamine in the brain through NO-enhanced oxidation of the catecholamine will almost certainly be manifested by diminished levels of the dopamine-derived brain pigment neuromelanin.The selective degeneration of melanized nigrostriatal dopaminergic neurons and attendant functional impairments of associated neuronal pathways are primary neuropathological manifestations of Parkinson's disease (PD).1 Neuronal degeneration in PD is accompanied by the progressive depletion of the neurotransmitter dopamine, as well as the pigment derived from its autoxidation, neuromelanin (1-3). Several mechanisms have been proposed to account for the selective vulnerability of the pigmented nigrostriatal dopaminergic neurons in PD, but the pathogenesis of this disease remains largely enigmatic. The neuropathology associated with PD has been attributed to oxidative stress resulting from the toxic effects of certain reactive intermediates of oxygen (ROI) (4), most notably the hydroxyl radical ( ⅐ OH), a highly reactive molecule generated by the interaction of hydrogen peroxide (H 2 O 2 ) with superoxide anion (O 2 . ), transition metals (Fe 2ϩ or Cu ϩ ), or nitric oxide (NO) (5, 6).The preferential targeting and destruction of nigrostriatal d...

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Section: Figsupporting

confidence: 76%

The Effects of Nitric Oxide on the Oxidations ofl-Dopa and Dopamine Mediated by Tyrosinase and Peroxidase

Nappi

Vass

2001

Journal of Biological Chemistry

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“…DA can auto-oxidize to the ortho-quinone that can readily react with cysteine residues in proteins such as DA transporters [38]. In synaptosomal preparations the, auto-oxidation of DA leads to the inhibition of DA uptake by the DAT [3] and inhibition of glutamate uptake by the glutamate transporter [2], and in the presence of tyrosinase, DA induces the covalent modification and inactivation of TH [41]. These harmful effects of DA auto-oxidation may result from the covalent modification of cysteinyl residues of proteins.…”

Section: Discussionmentioning

confidence: 99%

Disparity in the temporal appearance of methamphetamine-induced apoptosis and depletion of dopamine terminal markers in the striatum of mice

Zhu

Angulo

2005

Brain Research

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Methamphetamine (METH) causes damage in the striatum at pre-and post-synaptic sites. Exposure to METH induces long-term depletions of dopamine (DA) terminal markers such as tyrosine hydroxylase (TH) and DA transporters (DAT). METH also induces neuronal apoptosis in some striatal neurons. The purpose of this study is to demonstrate which occurs first, apoptosis of some striatal neurons or DA terminal toxicity in mice. This is important because the death of striatal neurons leaves the terminals in a state of deafferentation. A bolus injection (i.p.) of METH (30 mg/kg) induces apoptosis (TUNEL staining) in approximately 25% of neurons in the striatum at 24 h after METH. However, in contrast to apoptosis, depletion of TH (Western blotting) begins to appear at 24 h after METH in dorsal striatum while the ventral striatum is unaffected. The peak of TH depletion (approximately 80% decrease relative to control) occurs at 48 h after METH. Autoradiographic analysis of DAT sites showed that depletion begins to appear 24 h after METH and peaks at 2 days (approximately 60% depletion relative to control). Histological analysis of the induction of glial fibrillary acidic protein (GFAP) by METH in striatal astrocytes revealed an increase at 48 h after METH that peaked at 3 days. These data demonstrate that striatal apoptosis precedes the depletion (toxicity) of DA terminal markers in the striatum of mice, suggesting that the ensuing state of deafferentation of the DA terminals may contribute to their degeneration.

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“…It must be realized that metabolic deamination of dopamine and its O-methyl metabolite by MAO results in H 2 O 2 as a byproduct. Also, dopamine oxidation to dopamine quinone, stimulated by tyrosinase, is accompanied by the inactivation of tyrosine hydroxylase (226). Dopamine (aut)oxidation also probably explains the observed inactivation of parkin by dopamine (227), and dopamine quinone has been found to covalently modify Cys residues of the dopamine transporter (228).…”

Section: Role Of Oxidative Stress In the Pathogenesis Of Pd And Modelmentioning

confidence: 99%

Oxidative Stress and Neurotoxicity

Sayre

Perry

Smith

2007

Chem. Res. Toxicol.

754

494

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There is increasing awareness of the ubiquitous role of oxidative stress in neurodegenerative disease states. A continuing challenge is to be able to distinguish between oxidative changes that occur early in the disease from those that are secondary manifestations of neuronal degeneration. This perspective highlights the role of oxidative stress in Alzheimer's, Parkinson's, and Huntington's diseases, amyotrophic lateral sclerosis, and multiple sclerosis, neurodegenerative and neuroinflammatory disorders where there is evidence for a primary contribution of oxidative stress in neuronal death, as opposed to other diseases where oxidative stress more likely plays a secondary or by-stander role. We begin with a brief review of the biochemistry of oxidative stress as it relates to mechanisms that lead to cell death, and why the central nervous system is particularly susceptible to such mechanisms. Following a review of oxidative stress involvement in individual disease states, some conclusions are provided as to what further research should hope to accomplish in the field.

show abstract

Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase

Cited by 167 publications

References 32 publications

The Effects of Nitric Oxide on the Oxidations ofl-Dopa and Dopamine Mediated by Tyrosinase and Peroxidase

The Effects of Nitric Oxide on the Oxidations ofl-Dopa and Dopamine Mediated by Tyrosinase and Peroxidase

Disparity in the temporal appearance of methamphetamine-induced apoptosis and depletion of dopamine terminal markers in the striatum of mice

Oxidative Stress and Neurotoxicity

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