Glutamate induces autophagy via the two-pore channels in neural cells

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dc.citation.issue8
dc.citation.volume8
dc.contributor.authorPereira, Gustavo José da Silva [UNIFESP]
dc.contributor.authorAntonioli, Manuela
dc.contributor.authorHirata, Hanako [UNIFESP]
dc.contributor.authorUreshino, Rodrigo Portes [UNIFESP]
dc.contributor.authorNascimento, Aline Rosa [UNIFESP]
dc.contributor.authorBincoletto, Claudia [UNIFESP]
dc.contributor.authorVescovo, Tiziana
dc.contributor.authorPiacentini, Mauro
dc.contributor.authorFimia, Gian Maria
dc.contributor.authorSmaili, Soraya Soubhi [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.coverageOrchard Park
dc.date.accessioned2020-07-17T14:02:57Z
dc.date.available2020-07-17T14:02:57Z
dc.date.issued2017
dc.description.abstractNAADP (nicotinic acid adenine dinucleotide phosphate) has been proposed as a second messenger for glutamate in neuronal and glial cells via the activation of the lysosomal Ca2+ channels TPC1 and TPC2. However, the activities of glutamate that are mediated by NAADP remain unclear. In this study, we evaluated the effect of glutamate on autophagy in astrocytes at physiological, non-toxic concentration. We found that glutamate induces autophagy at similar extent as NAADP. By contrast, the NAADP antagonist NED-19 or SiRNA-mediated inhibition of TPC1/2 decreases autophagy induced by glutamate, confirming a role for NAADP in this pathway. The involvement of TPC1/2 in glutamate-induced autophagy was also confirmed in SHSY5Y neuroblastoma cells. Finally, we show that glutamate leads to a NAADP-dependent activation of AMPK, which is required for autophagy induction, while mTOR activity is not affected by this treatment. Taken together, our results indicate that glutamate stimulates autophagy via NAADP/TPC/AMPK axis, providing new insights of how Ca2+ signalling glutamate-mediated can control the cell metabolism in the central nervous system.en
dc.description.affiliationFed Univ Sao Paulo UNIFESP, Dept Pharmacol, Sao Paulo, Brazil
dc.description.affiliationUniv Roma Tor Vergata, Dept Biol, Rome, Italy
dc.description.affiliationNatl Inst Infect Dis IRCCS Lazzaro Spallanzani, Dept Epidemiol & Preclin Res, Rome, Italy
dc.description.affiliationUniv Salento, Dept Biol & Environm Sci & Technol DiSTeBA, Lecce, Italy
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP, Dept Pharmacol, Sao Paulo, Brazil
dc.description.provenanceMade available in DSpace on 2020-07-17T14:02:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2017. Added 1 bitstream(s) on 2020-07-17T14:35:22Z : No. of bitstreams: 1 WOS000395692000026.pdf: 1806837 bytes, checksum: 31deb8c014c1a1e2a60959f85bf0115e (MD5)en
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt
dc.description.sponsorshipRicerca Corrente and Finalizzata from the Italian Ministry of Health
dc.description.sponsorshipFIRB from MIUR
dc.description.sponsorshipFondazione Fibrosi Cistica
dc.description.sponsorshipAIRC
dc.description.sponsorshipIDFAPESP: 08/11515-3pt
dc.description.sponsorshipIDFAPESP: 13/20073-2pt
dc.description.sponsorshipIDFAPESP: 10/51647-6pt
dc.description.sponsorshipIDFAPESP: 13/01769-6pt
dc.format.extent12730-12740
dc.identifierhttps://dx.doi.org/10.18632/oncotarget.14404
dc.identifier.citationOncotarget. Orchard Park, v. 8, n. 8, p. 12730-12740, 2017.
dc.identifier.doi10.18632/oncotarget.14404
dc.identifier.fileWOS000395692000026.pdf
dc.identifier.issn1949-2553
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55097
dc.identifier.wosWOS:000395692000026
dc.language.isoeng
dc.publisherImpact Journals Llc
dc.relation.ispartofOncotarget
dc.rightsAcesso aberto
dc.subjectAutophagyen
dc.subjectGlutamateen
dc.subjectNAADPen
dc.subjectTwo-pore channelsen
dc.subjectAMPKen
dc.titleGlutamate induces autophagy via the two-pore channels in neural cellsen
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