A marked rise in 5-S-cysteinyl-dopamine levels in guinea-pig striatum following reserpine treatment

Fornstedt, Bodil; Carlsson, Arvid

doi:10.1007/bf01578755

Cited by 76 publications

(35 citation statements)

References 10 publications

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“…Striata from these mice were isolated as described above and assayed for cys-DA. Reserpine treatment increased cys-DA concentrations in the striatum by 135% at this time point, similar to that observed by Forstedt and Carlsson (Fornstedt & Carlsson, 1989).…”

Section: High Performance Liquid Chromatography (Hplc)supporting

confidence: 89%

“…In addition to the normal generation of ROS during synthesis and metabolism of dopamine, which result in the formation of hydrogen peroxide, auto-oxidation and ROS-or metal-catalyzed oxidation of cytosolic dopamine to form dopamine-quinones can cause further oxidative damage by reacting with sulfhydryl groups to form cysteinyl-adducts. Because cysteinyl residues are often present in the functional regions of many proteins, formation of dopamine-cysteinyl adducts at these sites can lead to serious alterations in protein function (Fornstedt & Carlsson, 1989;Hastings et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

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Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

Hatcher

Richardson

Guillot

et al. 2007

Experimental Neurology

132

107

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Numerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing Parkinson's disease (PD). Here, we provide evidence that the insecticide dieldrin causes specific oxidative damage in the nigrostriatal dopamine (DA) system. We report that exposure of mice to low levels of dieldrin for 30 days resulted in alterations in dopamine-handling as evidenced by a decrease in dopamine metabolites, DOPAC (31.7% decrease) and HVA (29.2% decrease) and significantly increased cysteinyl-catechol levels in the striatum. Furthermore, dieldrin resulted in a 53% decrease in total glutathione, an increase in the redox potential of glutathione, and a 90% increase in protein carbonyls. α-Synuclein protein expression was also significantly increased in the striatum (25% increase). Finally, dieldrin caused a significant decrease in striatal expression of the dopamine transporter as measured by 3 H-WIN 35,428 binding and 3 H-dopamine uptake. These alterations occurred in the absence of dopamine neuron loss in the substantia nigra pars compacta. These effects represent the ability of low doses of dieldrin to increase the vulnerability of nigrostriatal dopamine neurons by inducing oxidative stress and suggest that pesticide exposure may act as a promoter of PD. *Corresponding Author: Gary W. Miller, Ph.D., Emory University -Center for Neurodegenerative Disease, Whitehead Biomedical Research Building 505K, 615 Michael Street Atlanta, GA 30322, Phone: 404.712.8582, Fax: 404.727.3728, Email: gary.miller@emory.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Parkinson's disease (PD) is a chronic, progressive neurological disorder clinically characterized by resting tremor, bradykinesia, postural instability and rigidity (Marsden, 1984). Pathologically, PD presents as dopaminergic neuronal loss in the substantia nigra pars compacta (SNc), striatal depletion of the neurotransmitter dopamine (DA), the loss of neurochemical markers, such as the dopamine transporter (DAT), and the presence of Lewy bodies containing α-synuclein (Spillantini et al., 1997). Because only 5-10% of PD cases are thought to be primarily genetic in origin, investigation of the role of environmental factors in the pathogenesis of the disease is warranted (Dauer & Przedborski, 2003). NIH Public AccessNumerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing PD Le Couteur et al., 1999;Priyadarshi et al., 2000;Semchuk et al., 1991Semchuk et al., ,1992. In addition, a correlation between the presence of th...

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Section: High Performance Liquid Chromatography (Hplc)supporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

Hatcher

Richardson

Guillot

et al. 2007

Experimental Neurology

132

107

View full text Add to dashboard Cite

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“…In support of this latter possibility are data which show marked changes in DA metabolism following reserpine. These effects are particularly striking during the initial, acute period (within 1 hour) of reserpine administration (Elverfors and Nissbrandt, 1991;Fornstedt and Carlsson, 1989). However, at least one report has indicated that significant changes in the DOPAC : DA ratio persist at 24 hours post-reserpine (Starr etal., 1987).…”

Section: Discussionmentioning

confidence: 95%

The effect of reserpine treatment in vivo upon L-dopa and amphetamine evoked dopamine and DOPAC efflux in vitro from the corpus striatum of male rats

Dluzen

Liu

1994

J. Neural Transmission

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In the present experiment we tested the effects of L-DOPA and amphetamine upon dopamine and DOPAC efflux in vitro from superfused corpus striatal tissue fragments of male rats who had been pretreated with reserpine. Male rats were treated with reserpine (5 mg/kg) or its vehicle at 24 hours prior to sacrifice and superfusion of the corpus striatum. Two different modes of L-DOPA (5 microM) and amphetamine (10 microM) stimulation, a brief 10-minute and a continuous 60-minute infusion, were tested for their ability to evoke striatal dopamine and DOPAC efflux. Depletion of monoamine storage capacity as achieved with reserpine significantly reduced the amount of basal dopamine and DOPAC released from superfused striatal tissue fragments of male rats. Although basal release rates were significantly reduced, the amount of dopamine and DOPAC released in response to in vitro L-DOPA infusions (10 or 60 minute infusions) was equivalent between reserpine and vehicle treated animals. In contrast, amphetamine stimulated DA release was significantly reduced in male rats treated with reserpine. For both L-DOPA and amphetamine, significantly greater amounts of dopamine were obtained with the 60- versus 10-minute infusion modes. These results demonstrate that the capacity for L-DOPA, but not amphetamine, to evoke dopamine efflux is unaltered under conditions when monoamine storage ability is diminished.

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“…Based on the above information, one may hypothesize why the selective increase of DA oxidation exists in the age-related PD brain. Indeed, in substantia nigra, the increased oxidation of DA is observed by an increased ratio of free cysteinyl DA relative to DA (65,66). There is evidence suggesting that the neurons containing greater amounts of neuromelanin, a polymerization product of oxidized DA, are most susceptible to neuronal death in PD (67,68).…”

Section: Discussionmentioning

confidence: 98%

Dopamine Induces Apoptosis through an Oxidation-involved SAPK/JNK Activation Pathway

Luo¹,

Umegaki²,

Wang³

et al. 1998

Journal of Biological Chemistry

296

187

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Dopamine (DA) is a neurotransmitter, but it also exerts a neurotoxic effect under certain pathological conditions, including age-related neurodegeneration such as Parkinson's disease. By using both the 293 cell line and primary neonatal rat postmitotic striatal neuron cultures, we show here that DA induces apoptosis in a time-and concentration-dependent manner. Concomitant with the apoptosis, DA activates the JNK pathway, including increases in JNK activity, phosphorylation of c-Jun, and subsequent increase in c-Jun protein. This DA-induced JNK activation precedes apoptosis and is persistently sustained during the process of apoptosis. Transient expression of a dominant negative mutant SEK1(Lys 3 Arg), an upstream kinase of JNK, prevents both DA-induced JNK activation and apoptosis. A dominant negative c-Jun mutant FLAG⌬169 also reduces DA-induced apoptotic cell death. Anti-oxidants N-acetylcysteine and catalase, which serve as scavengers of reactive oxygen species generated by metabolic DA oxidation, effectively block DA-induced JNK activation and subsequent apoptosis. Thus, our data suggest that DA triggers an apoptotic death program through an oxidative stress-involved JNK activation signaling pathway. Given the fact that the anti-oxidative defense system declines during aging, this molecular event may be implicated in the age-related striatal neuronal cell loss and age-related dopaminergic neurodegenerative disorders, such as Parkinson's and Huntington's diseases.

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A marked rise in 5-S-cysteinyl-dopamine levels in guinea-pig striatum following reserpine treatment

Cited by 76 publications

References 10 publications

Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

The effect of reserpine treatment in vivo upon L-dopa and amphetamine evoked dopamine and DOPAC efflux in vitro from the corpus striatum of male rats

Dopamine Induces Apoptosis through an Oxidation-involved SAPK/JNK Activation Pathway

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