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

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

Author Pereira, Gustavo J. S. Autor UNIFESP Google Scholar
Antonioli, Manuela Google Scholar
Hirata, Hanako Autor UNIFESP Google Scholar
Ureshino, Rodrigo P. Autor UNIFESP Google Scholar
Nascimento, Aline R. Autor UNIFESP Google Scholar
Bincoletto, Claudia Autor UNIFESP Google Scholar
Vescovo, Tiziana Google Scholar
Piacentini, Mauro Google Scholar
Fimia, Gian Maria Google Scholar
Smaili, Soraya S. Autor UNIFESP Google Scholar
Abstract NAADP (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.
Keywords autophagy
glutamate
NAADP
two-pore channels
AMPK
xmlui.dri2xhtml.METS-1.0.item-coverage Orchard Park
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior (CAPES)
Ricerca Corrente and Finalizzata from the Italian Ministry of Health
FIRB from MIUR
Fondazione Fibrosi Cistica
AIRC
FAPESP
Grant number FAPESP: 08/11515-3
FAPESP: 13/20073-2
FAPESP: 10/51647-6
FAPESP: 13/01769-6
Date 2017
Published in Oncotarget. Orchard Park, v. 8, n. 8, p. 12730-12740, 2017.
ISSN 1949-2553 (Sherpa/Romeo, impact factor)
Publisher Impact Journals Llc
Extent 12730-12740
Origin http://dx.doi.org/10.18632/oncotarget.14404
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000395692000026
URI https://repositorio.unifesp.br/handle/11600/55097

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