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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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.
Total Authors: 10
Document type: Journal article
Source: ONCOTARGET; v. 8, n. 8, p. 12730-12740, 2017.
Web of Science Citations: 15

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)

FAPESP's process: 13/01769-6 - Effect of NAADP in autophagic signaling regulated by mTOR (mammalian Target of Rapamycin) in astrocytes
Grantee:Gustavo José da Silva Pereira
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 13/20073-2 - Autophagy as a protective mechanism in senescent rats
Grantee:Soraya Soubhi Smaili
Support type: Regular Research Grants
FAPESP's process: 08/11515-3 - Mechanisms of Intracellular Calcium Signaling int the Modulation of Apoptosis and Autophagy
Grantee:Soraya Soubhi Smaili
Support type: Regular Research Grants