R -(−)-Deprenyl Inhibits Monocytic THP-1 Cell Neurotoxicity Independently of Monoamine Oxidase Inhibition
Identifieur interne : 003453 ( Main/Exploration ); précédent : 003452; suivant : 003454R -(−)-Deprenyl Inhibits Monocytic THP-1 Cell Neurotoxicity Independently of Monoamine Oxidase Inhibition
Auteurs : Andis Klegeris [Canada] ; Patrick L. Mcgeer [Canada]Source :
- Experimental Neurology [ 0014-4886 ] ; 2000.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Alzheimer Disease (drug therapy), Alzheimer Disease (metabolism), Alzheimer's disease, Antidepressant agent, Antiparkinson agent, DNA Primers, Gene Expression Regulation, Enzymologic, Human, Humans, MAO B inhibitor, Mechanism of action, Monoamine Oxidase (genetics), Monoamine Oxidase (metabolism), Monoamine Oxidase Inhibitors (pharmacology), Monocytes (cytology), Monocytes (enzymology), Nerve Degeneration (drug therapy), Nerve Degeneration (metabolism), Neuroblastoma, Neurons (drug effects), Neurons (enzymology), Neuroprotective agent, Neurotoxins (metabolism), Parkinson Disease (drug therapy), Parkinson Disease (metabolism), Parkinson disease, Parkinson's disease, Phenelzine, RNA, Messenger (analysis), RNA-directed DNA polymerase, Selegiline, Selegiline (pharmacology), Tumor Cells, Cultured, deprenyl, human microglia, monoamine oxidase, neurodegeneration, neuroprotection, selegiline.
- MESH :
- chemical , analysis : RNA, Messenger.
- chemical , genetics : Monoamine Oxidase.
- chemical , metabolism : Monoamine Oxidase, Neurotoxins.
- chemical , pharmacology : Monoamine Oxidase Inhibitors, Selegiline.
- chemical : DNA Primers.
- cytology : Monocytes.
- drug effects : Neurons.
- drug therapy : Alzheimer Disease, Nerve Degeneration, Parkinson Disease.
- enzymology : Monocytes, Neurons.
- metabolism : Alzheimer Disease, Nerve Degeneration, Parkinson Disease.
- Gene Expression Regulation, Enzymologic, Humans, Neuroblastoma, Tumor Cells, Cultured.
Abstract
R-(−)-Deprenyl (deprenyl, selegiline), a monoamine oxidase B (MAO-B) inhibitor, delays progression of Parkinson's disease. This action could be mediated by inhibition of MAO-B but there may also be unrelated mechanisms. Direct neuroprotective and antiapoptotic actions of deprenyl have previously been observed in vitro. Here we describe an antineurotoxic action of deprenyl which is independent of direct neuronal effects. We employed a previously described assay in which human neuroblastoma SH-SY5Y cells are exposed to cell-free supernatants of stimulated human monocytic THP-1 cells. Deprenyl reduced the secretion of neurotoxic products by such stimulated cells in a concentration-dependent manner, while the MAO inhibitors iproniazid, isocarboxazid, nialamide, tranylcypromine, phenelzine, and clorgyline were without effect. No antineurotoxic action was observed when deprenyl was added directly to SH-SY5Y cells. Messenger RNAs for MAO-A and MAO-B were not detected in THP-1 cells by reverse transcriptase-polymerase chain reaction analysis of total RNA extracts. Such mRNAs were easily detected in extracts of SH-SY5Y cells under comparable conditions. MAO enzymatic activity was also undetectable in THP-1 cell lysates, while it was readily observed in SH-SY5Y cells. It was concluded that the effect of deprenyl on THP-1 cells was not mediated by MAO and that deprenyl itself was not protecting neurons. These data suggest that deprenyl may have utility in neurodegenerative diseases due to its antineurotoxic actions.
Url:
DOI: 10.1006/exnr.2000.7517
Affiliations:
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Le document en format XML
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<term>Antiparkinson agent</term>
<term>DNA Primers</term>
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<front><div type="abstract" xml:lang="en">R-(−)-Deprenyl (deprenyl, selegiline), a monoamine oxidase B (MAO-B) inhibitor, delays progression of Parkinson's disease. This action could be mediated by inhibition of MAO-B but there may also be unrelated mechanisms. Direct neuroprotective and antiapoptotic actions of deprenyl have previously been observed in vitro. Here we describe an antineurotoxic action of deprenyl which is independent of direct neuronal effects. We employed a previously described assay in which human neuroblastoma SH-SY5Y cells are exposed to cell-free supernatants of stimulated human monocytic THP-1 cells. Deprenyl reduced the secretion of neurotoxic products by such stimulated cells in a concentration-dependent manner, while the MAO inhibitors iproniazid, isocarboxazid, nialamide, tranylcypromine, phenelzine, and clorgyline were without effect. No antineurotoxic action was observed when deprenyl was added directly to SH-SY5Y cells. Messenger RNAs for MAO-A and MAO-B were not detected in THP-1 cells by reverse transcriptase-polymerase chain reaction analysis of total RNA extracts. Such mRNAs were easily detected in extracts of SH-SY5Y cells under comparable conditions. MAO enzymatic activity was also undetectable in THP-1 cell lysates, while it was readily observed in SH-SY5Y cells. It was concluded that the effect of deprenyl on THP-1 cells was not mediated by MAO and that deprenyl itself was not protecting neurons. These data suggest that deprenyl may have utility in neurodegenerative diseases due to its antineurotoxic actions.</div>
</front>
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