Tyrosine mRNA is expressed in human substantia nigra

Xu, Yimei; Stokes, Alan H.; Freeman, Willard M.; Kumer, Sean C.; Vogt, Brent A.; Vrana, Kent E.

doi:10.1016/s0169-328x(96)00308-7

Cited by 202 publications

(152 citation statements)

References 20 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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“…11,12 Tyrosinase is also involved in neuromelanin formation in the brain and neurodegeneration associated with Parkinson's disease. 13,14 Thus, tyrosinase inhibitors have attracted increasing attention. In principle, tyrosinase inhibitors have potential applications in the agricultural, cosmetic and pharmaceutical industry.…”

Section: Hydroxylation Of L-tyrosine To L-3-(34-dihydroxyphenyl)-alamentioning

confidence: 99%

“…All the compounds have been fully characterized by 1 H NMR, 13 C NMR and HRMS. Inhibitory activity of hydroxypyridinone derivatives 6 and 12 on monophenolase activity of mushroom tyrosinase was investigated using L-tyrosine as a substrate.…”

Section: Hydroxylation Of L-tyrosine To L-3-(34-dihydroxyphenyl)-alamentioning

confidence: 99%

Design and synthesis of novel hydroxypyridinone derivatives as potential tyrosinase inhibitors

Zhao

Zhang

Dong

et al. 2016

Bioorganic & Medicinal Chemistry Letters

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Two groups of novel hydroxypyridinone derivatives 6(a-e) and 12(a-c),were designed as potential tyrosinase inhibitors, and synthesized using kojic acid as a starting material. The tyrosinase inhibitory activity of these two groups was demonstrated to be potent, especially compounds 6e and 12a, whose IC 50 values for monophenolase activity were 1.95 µM and 2.79 µM, respectively. Both of these values are lower than that of kojic acid (IC 50 = 12.50 µM). Compounds 6e and 12a were investigated for the inhibitory effect on diphenolase activity. The results showed that the inhibitory mechanism of these two compounds was reversible and that the inhibitory type was a competitive-uncompetitive mixed-type. The values of IC 50 of 6e and 12a on the diphenolase activity of tyrosinase were determined to be 8.97 µM and 26.20 µM, respectively. The inhibitory constants (K I and K IS ) of 6e were determined as 17.17 µM and 22.09 µM, respectively; and the K I and K IS values of 12a were 34.41 µM and 79.02 µM, respectively. Compound 6e showed a greater ability to reduce copper and a stronger copper chelating ability than kojic acid.

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“…For example, tyrosinase mRNA is also expressed in brain tissue. 22 Low levels of ␣-fetoprotein expression were also detected in normal liver tissue, suggesting that nonmalignant progenitor liver cells express ␣-fetoprotein. Therefore, the identification and development of more specific promoters is crucial.…”

Section: Discussionmentioning

confidence: 99%

Targeting and eradicating cancer cells by a prostate-specific vector carrying the diphtheria toxin A gene

Pang

2000

Cancer Gene Ther

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Prostate cancer is the most commonly diagnosed malignancy in American men. Developing gene therapy for prostate cancer is important, because there is no effective treatment for patients in the advanced stages of this disease. A tissue-specific promoter to transcriptionally target cancer cells is a promising approach for gene therapy of prostate cancer. We previously constructed a prostate tissue-specific promoter based on the proximal promoter and the upstream regulatory sequence of the prostate-specific antigen gene. In the experiments described here, we modified our prostate-specific promoter to drive the A domain of the diphtheria toxin gene (DTA) in a plasmid vector. The plasmid vector can be efficiently transfected into cell lines, using a liposome-mediated transfection method. In the transfected prostate cell line, LNCaP, the DTA gene was actively transcribed, and significant inhibition of protein synthesis and cytopathic effects was observed. However, no pathogenic effects were apparent in the control cell lines. The highly specific and efficient cytopathicity of the DTA gene vector is therefore potentially useful for systemic treatment of patients with metastatic prostate cancer. Cancer Gene Therapy (2000) 7, 991-996

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Tyrosine mRNA is expressed in human substantia nigra

Cited by 202 publications

References 20 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

Design and synthesis of novel hydroxypyridinone derivatives as potential tyrosinase inhibitors

Targeting and eradicating cancer cells by a prostate-specific vector carrying the diphtheria toxin A gene

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