TY  - CONF
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Ćirić, Darko
AU  - Martinović, Tamara
AU  - Jovanović, Maja
AU  - Isaković, Aleksandra
AU  - Marković, Ivanka
AU  - Zogović, Nevena
AU  - Foretz, Mark
AU  - Rabanal-Ruiz, Yoana
AU  - Korolchuk, Viktor
AU  - Trajković, Vladimir
PY  - 2019
UR  - https://www.fens.org/news-activities/fens-and-societies-calendar/meeting-event/fens-regional-meeting-2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6357
AB  - We investigated the effect of excitotoxic glutamate on nutrient starvation-induced autophagy, a process of lysosome-mediated degradation of cellular macromolecules and organelles. Incubation of SH-SY5Y human neuroblastoma cell line in glucose/amino acid/serum-free Hank Balanced Salt solution synergized with glutamate in causing energy stress and excitotoxic necrosis. Glutamate inhibited starvation-induced autophagy, as demonstrated by decreased intracellular acidification, lower LC3 punctuation, reduced conversion of LC3-I to LC3-II, reduced expression of autophagy activators beclin-1 and ATG5, increased
levels of the selective autophagic target NBR1, and decline in the number of autophagic vesicles observed by transmission electron microscopy. NMDA antagonist memantine restored LC3B-II accumulation in starved cells exposed to glutamate, indicating that glutamate exerts its inhibitory role on autophagy by activating NMDA receptors. The modulation of mTOR, the negative regulator of autophagy, was not responsible for glutamate-mediated autophagy inhibition during starvation. On the other hand, glutamate downregulated starvation-induced activation of the intracellular energy sensor AMP-activated protein
kinase (AMPK). This was associated with reduced mRNA expression of autophagy transcription factors FOXO3 and ATF4, as well as molecules involved in autophagy process (ULK1, ATG13, FIP200, ATG14, beclin-1, ATG5, ATG12, SQSTM1). The ability of glutamate to repress transcription of autophagy genes in starved cells was partly mediated by AMPK downregulation. Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, as well as genetic or pharmacological autophagy induction by TFEB overexpression or lithium chloride, rescued cells from glutamate-mediated excitoxicity. These data indicate that transcriptional inhibition of AMPK-dependent autophagy is involved in glutamate-mediated excitotoxicity during nutrient deprivation in vitro.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Autophagy regulation and its role in glutamate excitotoxicity during nutrient stress
SP  - 144
EP  - 144
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6357
ER  - 

@conference{
author = "Vučićević, Ljubica and Misirkić Marjanović, Maja and Ćirić, Darko and Martinović, Tamara and Jovanović, Maja and Isaković, Aleksandra and Marković, Ivanka and Zogović, Nevena and Foretz, Mark and Rabanal-Ruiz, Yoana and Korolchuk, Viktor and Trajković, Vladimir",
year = "2019",
abstract = "We investigated the effect of excitotoxic glutamate on nutrient starvation-induced autophagy, a process of lysosome-mediated degradation of cellular macromolecules and organelles. Incubation of SH-SY5Y human neuroblastoma cell line in glucose/amino acid/serum-free Hank Balanced Salt solution synergized with glutamate in causing energy stress and excitotoxic necrosis. Glutamate inhibited starvation-induced autophagy, as demonstrated by decreased intracellular acidification, lower LC3 punctuation, reduced conversion of LC3-I to LC3-II, reduced expression of autophagy activators beclin-1 and ATG5, increased
levels of the selective autophagic target NBR1, and decline in the number of autophagic vesicles observed by transmission electron microscopy. NMDA antagonist memantine restored LC3B-II accumulation in starved cells exposed to glutamate, indicating that glutamate exerts its inhibitory role on autophagy by activating NMDA receptors. The modulation of mTOR, the negative regulator of autophagy, was not responsible for glutamate-mediated autophagy inhibition during starvation. On the other hand, glutamate downregulated starvation-induced activation of the intracellular energy sensor AMP-activated protein
kinase (AMPK). This was associated with reduced mRNA expression of autophagy transcription factors FOXO3 and ATF4, as well as molecules involved in autophagy process (ULK1, ATG13, FIP200, ATG14, beclin-1, ATG5, ATG12, SQSTM1). The ability of glutamate to repress transcription of autophagy genes in starved cells was partly mediated by AMPK downregulation. Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, as well as genetic or pharmacological autophagy induction by TFEB overexpression or lithium chloride, rescued cells from glutamate-mediated excitoxicity. These data indicate that transcriptional inhibition of AMPK-dependent autophagy is involved in glutamate-mediated excitotoxicity during nutrient deprivation in vitro.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Autophagy regulation and its role in glutamate excitotoxicity during nutrient stress",
pages = "144-144",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6357"
}

Vučićević, L., Misirkić Marjanović, M., Ćirić, D., Martinović, T., Jovanović, M., Isaković, A., Marković, I., Zogović, N., Foretz, M., Rabanal-Ruiz, Y., Korolchuk, V.,& Trajković, V.. (2019). Autophagy regulation and its role in glutamate excitotoxicity during nutrient stress. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society., 144-144.
https://hdl.handle.net/21.15107/rcub_ibiss_6357

Vučićević L, Misirkić Marjanović M, Ćirić D, Martinović T, Jovanović M, Isaković A, Marković I, Zogović N, Foretz M, Rabanal-Ruiz Y, Korolchuk V, Trajković V. Autophagy regulation and its role in glutamate excitotoxicity during nutrient stress. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:144-144.
https://hdl.handle.net/21.15107/rcub_ibiss_6357 .

Vučićević, Ljubica, Misirkić Marjanović, Maja, Ćirić, Darko, Martinović, Tamara, Jovanović, Maja, Isaković, Aleksandra, Marković, Ivanka, Zogović, Nevena, Foretz, Mark, Rabanal-Ruiz, Yoana, Korolchuk, Viktor, Trajković, Vladimir, "Autophagy regulation and its role in glutamate excitotoxicity during nutrient stress" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):144-144,
https://hdl.handle.net/21.15107/rcub_ibiss_6357 .