A study of oxidized glutathione as an index of oxidant stress in the central nervous system.
Item
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Title
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A study of oxidized glutathione as an index of oxidant stress in the central nervous system.
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Identifier
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AAI9009786
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identifier
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9009786
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Creator
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Spina, Mary Beth.
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Contributor
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Adviser: Gerald Cohen
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Date
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1989
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience | Biology, General
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Abstract
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The oxidation of dopamine by monoamine oxidase generates hydrogen peroxide, which is potentially toxic to neurons. In the presence of hydrogen peroxide, reduced glutathione (GSH) is oxidized to glutathione disulfide (GSSG) by GSH peroxidase. A rise in the steady state level can be used as an index of oxidative stress. Dopamine metabolism was provoked both in vitro and in vivo and GSSG was measured.;Incubation of striatal synaptosomes with L-dopa or dopamine in either the presence or absence of 10 uM reserpine resulted in a rise in the level of (GSSG) within the isolated tissue pellet. This rise was dependent upon the concentration of DA or L-dopa. With 1.0 mM L-dopa in the presence of reserpine, GSSG was elevated by 7.0 {dollar}\pm{dollar} 0.7 pmol/mg original striatal tissue; while, 10 uM DA in the presence of reserpine, elevated GSSG by 4.1 {dollar}\pm{dollar} 0.5 pmol/mg original striatal tissue. In the presence of clorgyline or pargyline (monoamine oxidase inhibitors) the rise in GSSG caused by DA or L-dopa was suppressed. These data show that the metabolism of DA can evoke a significant rise in the level of GSSG.;Experiments were also conducted in vivo in which mice were treated with either reserpine or haloperidol to induce DA metabolism, and GSSG levels were measured in the striata. Reserpine elevated GSSG by 6.1 {dollar}\pm{dollar} 0.6 uM; and haloperidol increased GSSG by 12.3 {dollar}\pm{dollar} 1.0 uM. The increase produced by reserpine was seen in the striatum but not in the frontal cortex, which receives a much sparser innervation by dopamine terminals. Similarly, when the dopamine terminals were destroyed in the striatum by 6-hydroxydopamine, the increase in GSSG caused by haloperidol was suppressed. Both an MAO-A inhibitor (clorgyline) and an MAO-B inhibitor (deprenyl) significantly suppressed the rise in GSSG caused by reserpine or haloperidol.;The data presented in this thesis indicates that the turnover of dopamine both in vitro and in vivo is associated with a significant oxidant stress. The data may shed some light on disease states which are accompanied by increased turnover of monoamines, such as Parkinson's disease.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
