ParkinsonCanadaV1, PascalFrancis, Curation, bibRecord, 000072

R-(-)-deprenyl inhibits monocytic THP-1 cell neurotoxicity independently of monoamine oxidase inhibition

Identifieur interne : 000072 ( PascalFrancis/Curation ); précédent : 000071; suivant : 000073

R-(-)-deprenyl inhibits monocytic THP-1 cell neurotoxicity independently of monoamine oxidase inhibition

Auteurs : Andis Klegeris [Canada] ; Patrick L. Mcgeer [Canada]

Source :

Experimental neurology : (Print) [ 0014-4886 ] ; 2000.

RBID : Pascal:01-0095078

Descripteurs français

Pascal (Inist)
- Parkinson maladie, Sélégiline, Phénelzine, IMAO B, Neuroprotecteur, Mécanisme action, Homme, RNA-directed DNA polymerase, Antiparkinsonien, Antidépresseur.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Antidepressant agent, Antiparkinson agent, Human, MAO B inhibitor, Mechanism of action, Neuroprotective agent, Parkinson disease, Phenelzine, RNA-directed DNA polymerase, Selegiline.

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.

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A11	`01`	`1`		`@1 KLEGERIS (Andis)`
A11	`02`	`1`		`@1 MCGEER (Patrick L.)`
A14	`01`			`@1 Kinsmen Laboratory of Neurological Research, University of British Columbia @2 Vancouver, British Columbia V6T 1Z3 @3 CAN @Z 1 aut. @Z 2 aut.`
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C07	`07`	`X`	`FRE`	`@0 Extrapyramidal syndrome @5 40`
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C07	`07`	`X`	`SPA`	`@0 Extrapiramidal síndrome @5 40`
C07	`08`	`X`	`FRE`	`@0 Encéphale pathologie @5 41`
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C07	`08`	`X`	`SPA`	`@0 Encéfalo patología @5 41`
C07	`09`	`X`	`FRE`	`@0 Tumeur maligne @5 42`
C07	`09`	`X`	`ENG`	`@0 Malignant tumor @5 42`
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C07	`10`	`X`	`FRE`	`@0 Système nerveux sympathique pathologie @5 43`
C07	`10`	`X`	`ENG`	`@0 Autonomic neuropathy @5 43`
C07	`10`	`X`	`SPA`	`@0 Sistema nervioso simpático patología @5 43`
N21				`@1 064`

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Pascal:01-0095078

Le document en format XML

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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>
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<s2>FE</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Nucleotidyltransferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Transferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Transferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Transferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Enzyme</s0>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Enzyme</s0>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Enzima</s0>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Système nerveux pathologie</s0>
<s5>37</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Nervous system diseases</s0>
<s5>37</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Sistema nervioso patología</s0>
<s5>37</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Système nerveux central pathologie</s0>
<s5>38</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Central nervous system disease</s0>
<s5>38</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0>
<s5>38</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Maladie dégénérative</s0>
<s5>39</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Degenerative disease</s0>
<s5>39</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0>
<s5>39</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Extrapyramidal syndrome</s0>
<s5>40</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0>
<s5>40</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0>
<s5>40</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE"><s0>Encéphale pathologie</s0>
<s5>41</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>Cerebral disorder</s0>
<s5>41</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA"><s0>Encéfalo patología</s0>
<s5>41</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE"><s0>Tumeur maligne</s0>
<s5>42</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG"><s0>Malignant tumor</s0>
<s5>42</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA"><s0>Tumor maligno</s0>
<s5>42</s5>
</fC07>
<fC07 i1="10" i2="X" l="FRE"><s0>Système nerveux sympathique pathologie</s0>
<s5>43</s5>
</fC07>
<fC07 i1="10" i2="X" l="ENG"><s0>Autonomic neuropathy</s0>
<s5>43</s5>
</fC07>
<fC07 i1="10" i2="X" l="SPA"><s0>Sistema nervioso simpático patología</s0>
<s5>43</s5>
</fC07>
<fN21><s1>064</s1>
</fN21>
</pA>
</standard>
</inist>
</record>

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	La maladie de Parkinson au Canada (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

La maladie de Parkinson au Canada (serveur d'exploration)

R-(-)-deprenyl inhibits monocytic THP-1 cell neurotoxicity independently of monoamine oxidase inhibition

R-(-)-deprenyl inhibits monocytic THP-1 cell neurotoxicity independently of monoamine oxidase inhibition

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