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The protective effect of tianeptine on Gp120-induced apoptosis in astroglial cells: role of GS and NOS, and NF-κB suppression

Identifieur interne : 000230 ( France/Analysis ); précédent : 000229; suivant : 000231

The protective effect of tianeptine on Gp120-induced apoptosis in astroglial cells: role of GS and NOS, and NF-κB suppression

Auteurs : Elzbieta Janda [Italie] ; Valeria Visalli [Italie] ; Carmela Colica [Italie] ; Serafina Aprigliano [Italie] ; Vincenzo Musolino [Italie] ; Nuria Vadala [Italie] ; Carolina Muscoli [Italie] ; Iolanda Sacco [Italie] ; Michelangelo Iannone [Italie] ; Domenicantonio Rotiroti [Italie] ; Michael Spedding [France] ; Vincenzo Mollace [Italie]

Source :

RBID : Pascal:12-0015370

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English descriptors

Abstract

BACKGROUND AND PURPOSE Tianeptine is an antidepressant affecting the glutamatergic system. In spite of its proven clinical efficacy, molecular effects of tianeptine are not entirely clear. Tianeptine modulates cytokine expression in the CNS and protects the hippocampus from chronic stress effects. HIV infection is associated with inflammation and neuronal loss, causing HIV-associated dementia (HAD). The human immunodeficiency virus type-1 glycoprotein gp120 has been proposed as a likely aetiological agent of HAD. In this study, we determined whether tianeptine protects astroglial cells from the neurodegenerative effects of gp120. EXPERIMENTAL APPROACH Human astroglial cells were treated with gp120 and tianeptine, and viability and apoptosis was monitored by TUNEL, annexin V, and activated caspase-3 staining and flow cytometry. Protein levels of glutamine synthase (GS), inducible and constitutive nitric oxide synthases (iNOS, cNOS) and nuclear factor κB (NF-κB) pathway were determined by Western blot analysis. The respective activities were assessed indirectly by measuring glutamine and nitrite concentrations or by luciferase reporter assays. KEY RESULTS Tianeptine showed an anti-apoptotic effect and prevented caspase-3 activation by gp120. The mechanism of tianeptine's action involved GS and cNOS stabilization and iNOS suppression. Moreover, tianeptine increased IκB-α levels in the absence of gp120 and blocked its degradation in response to gp120. This correlated with the suppression of basal and gp120-induced NF-κB transcriptional activity. CONCLUSIONS AND IMPLICATIONS Tianeptine clearly exerts neuroprotective effects in vitro by suppressing the molecular pro-inflammatory effects of gp120. Studies in animal models should be performed to evaluate the potential of tianeptine as a treatment for HAD.


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Pascal:12-0015370

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<title level="j" type="main">British journal of pharmacology</title>
<title level="j" type="abbreviated">Br. j. pharmacol.</title>
<idno type="ISSN">0007-1188</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Antidepressant agent</term>
<term>Apoptosis</term>
<term>Cell death</term>
<term>Drug</term>
<term>In vitro</term>
<term>Inflammation</term>
<term>Neuroprotection</term>
<term>Nitric oxide</term>
<term>Prevention</term>
<term>Psychotropic</term>
<term>Tianeptine</term>
<term>Transcription factor NFκB</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Prévention</term>
<term>Tianeptine</term>
<term>Apoptose</term>
<term>Mort cellulaire</term>
<term>In vitro</term>
<term>Facteur transcription NFκB</term>
<term>Monoxyde d'azote</term>
<term>Antidépresseur</term>
<term>Médicament</term>
<term>Neuroprotection</term>
<term>Inflammation</term>
<term>Psychotrope</term>
<term>Protéine gp120</term>
<term>Glycoprotéine gp120</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Médicament</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">BACKGROUND AND PURPOSE Tianeptine is an antidepressant affecting the glutamatergic system. In spite of its proven clinical efficacy, molecular effects of tianeptine are not entirely clear. Tianeptine modulates cytokine expression in the CNS and protects the hippocampus from chronic stress effects. HIV infection is associated with inflammation and neuronal loss, causing HIV-associated dementia (HAD). The human immunodeficiency virus type-1 glycoprotein gp120 has been proposed as a likely aetiological agent of HAD. In this study, we determined whether tianeptine protects astroglial cells from the neurodegenerative effects of gp120. EXPERIMENTAL APPROACH Human astroglial cells were treated with gp120 and tianeptine, and viability and apoptosis was monitored by TUNEL, annexin V, and activated caspase-3 staining and flow cytometry. Protein levels of glutamine synthase (GS), inducible and constitutive nitric oxide synthases (iNOS, cNOS) and nuclear factor κB (NF-κB) pathway were determined by Western blot analysis. The respective activities were assessed indirectly by measuring glutamine and nitrite concentrations or by luciferase reporter assays. KEY RESULTS Tianeptine showed an anti-apoptotic effect and prevented caspase-3 activation by gp120. The mechanism of tianeptine's action involved GS and cNOS stabilization and iNOS suppression. Moreover, tianeptine increased IκB-α levels in the absence of gp120 and blocked its degradation in response to gp120. This correlated with the suppression of basal and gp120-induced NF-κB transcriptional activity. CONCLUSIONS AND IMPLICATIONS Tianeptine clearly exerts neuroprotective effects in vitro by suppressing the molecular pro-inflammatory effects of gp120. Studies in animal models should be performed to evaluate the potential of tianeptine as a treatment for HAD.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>France</li>
<li>Italie</li>
</country>
</list>
<tree>
<country name="Italie">
<noRegion>
<name sortKey="Janda, Elzbieta" sort="Janda, Elzbieta" uniqKey="Janda E" first="Elzbieta" last="Janda">Elzbieta Janda</name>
</noRegion>
<name sortKey="Aprigliano, Serafina" sort="Aprigliano, Serafina" uniqKey="Aprigliano S" first="Serafina" last="Aprigliano">Serafina Aprigliano</name>
<name sortKey="Colica, Carmela" sort="Colica, Carmela" uniqKey="Colica C" first="Carmela" last="Colica">Carmela Colica</name>
<name sortKey="Iannone, Michelangelo" sort="Iannone, Michelangelo" uniqKey="Iannone M" first="Michelangelo" last="Iannone">Michelangelo Iannone</name>
<name sortKey="Mollace, Vincenzo" sort="Mollace, Vincenzo" uniqKey="Mollace V" first="Vincenzo" last="Mollace">Vincenzo Mollace</name>
<name sortKey="Mollace, Vincenzo" sort="Mollace, Vincenzo" uniqKey="Mollace V" first="Vincenzo" last="Mollace">Vincenzo Mollace</name>
<name sortKey="Muscoli, Carolina" sort="Muscoli, Carolina" uniqKey="Muscoli C" first="Carolina" last="Muscoli">Carolina Muscoli</name>
<name sortKey="Musolino, Vincenzo" sort="Musolino, Vincenzo" uniqKey="Musolino V" first="Vincenzo" last="Musolino">Vincenzo Musolino</name>
<name sortKey="Rotiroti, Domenicantonio" sort="Rotiroti, Domenicantonio" uniqKey="Rotiroti D" first="Domenicantonio" last="Rotiroti">Domenicantonio Rotiroti</name>
<name sortKey="Sacco, Iolanda" sort="Sacco, Iolanda" uniqKey="Sacco I" first="Iolanda" last="Sacco">Iolanda Sacco</name>
<name sortKey="Vadala, Nuria" sort="Vadala, Nuria" uniqKey="Vadala N" first="Nuria" last="Vadala">Nuria Vadala</name>
<name sortKey="Visalli, Valeria" sort="Visalli, Valeria" uniqKey="Visalli V" first="Valeria" last="Visalli">Valeria Visalli</name>
<name sortKey="Visalli, Valeria" sort="Visalli, Valeria" uniqKey="Visalli V" first="Valeria" last="Visalli">Valeria Visalli</name>
</country>
<country name="France">
<noRegion>
<name sortKey="Spedding, Michael" sort="Spedding, Michael" uniqKey="Spedding M" first="Michael" last="Spedding">Michael Spedding</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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