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

Autor(es)

Pereira, Gustavo J. S. ; Antonioli, Manuela ; Hirata, Hanako ; Ureshino, Rodrigo P. ; Nascimento, Aline R. ; Bincoletto, Claudia ; Vescovo, Tiziana ; Piacentini, Mauro ; Fimia, Gian Maria ; Smaili, Soraya S.

• Tipo de documento: Artigo Científico
• Fonte: ONCOTARGET; v. 8, n. 8, p. 12730-12740, 2017.
• Citações Web of Science: 15

Resumo

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. (AU)

• Processo FAPESP: 08/11515-3 - Mecanismos de sinalização de cálcio intracelular na Modulação da Apoptose e da Autofagia
• Beneficiário: Soraya Soubhi Smaili
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/01769-6 - Estudo do mecanismo de sinalização do NAADP na via autofágica regulada pela mTOR (mammalian Target of Rapamycin) em astrócitos
• Beneficiário: Gustavo José da Silva Pereira
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 10/51647-6 - Atividade antitumoral de compostos paladaciclos em linhagem celular estabelecida de osteossarcoma humano: vias de sinalizacao de calcio na morte celular programada e autofagia.
• Beneficiário: Claudia Bincoletto Trindade
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/20073-2 - Estudo da autofagia no processo de proteção celular de ratas senescentes
• Beneficiário: Soraya Soubhi Smaili
• Modalidade de apoio: Auxílio à Pesquisa - Regular