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Glutamate-mediated autophagy inhibition intensifies excitotoxic death of nutrient-deprived SH-SY5Y neuroblastoma cells
dc.creator | Misirkić Marjanović, Maja | |
dc.creator | Vučićević, Ljubica | |
dc.creator | Ćirić, Darko | |
dc.creator | Martinović, Tamara | |
dc.creator | Jovanović, Maja | |
dc.creator | Isaković, Aleksandra | |
dc.creator | Marković, Ivanka | |
dc.creator | Trajković, Vladimir | |
dc.date.accessioned | 2024-04-08T10:43:01Z | |
dc.date.available | 2024-04-08T10:43:01Z | |
dc.date.issued | 2019 | |
dc.identifier.uri | http://radar.ibiss.bg.ac.rs/handle/123456789/6661 | |
dc.description.abstract | We investigated the role of autophagy in glutamate excitotoxicity during nutrient deprivation in vitro. Lack of serum, amino acids, and glucose markedly increased the sensitivity of SH-SY5Y human neuroblastoma cell line to glutamate-induced excitotoxic necrosis. Glutamate suppressed starvation-triggered autophagic response, as confirmed by diminished intracellular acidification, lower LC3 punctuation and conversion of LC3I to autophagosome associated LC3II, reduced levels of autophagy activators beclin-1 and ATG5, increased levels of the selective autophagic target NBR1, and reduced appearance of autophagic vesicles observed by transmission electron microscopy. Glutamate reduced starvation-triggered phosphorylation of the intracellular energy sensor AMP-activated protein kinase (AMPK), without affecting the activity of mammalian target of rapamycin complex1 as a major negative regulator of autophagy. Similar results were shown on PC12 cells, which are often exploited as a model for excitotoxicity. We also detected reduced mRNA expression of autophagy transcription factors FOXO3 and ATF4, as well as molecules involved in autophagy initiation (ULK1, ATG13, FIP200), autophagosome nucleation/elongation (ATG14, beclin 1, ATG5, ATG12), and the autophagy cargo delivery to autophagosmes (SQSTM1/p62). Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, reduced the sensitivity of nutrient-deprived SH-SY5Y cells to glutamate dependent autophagy is involved in glutamate-mediated excitotoxicity during nutrient deprivation in vitro. | sr |
dc.language.iso | en | sr |
dc.publisher | Nordic Autophagy Society | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41025/RS// | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173053/RS// | sr |
dc.rights | openAccess | sr |
dc.source | 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Nederlands | sr |
dc.title | Glutamate-mediated autophagy inhibition intensifies excitotoxic death of nutrient-deprived SH-SY5Y neuroblastoma cells | sr |
dc.type | conferenceObject | sr |
dc.rights.license | ARR | sr |
dc.rights.holder | © 2019 by the Nordic Autophagy Society | sr |
dc.description.other | 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands. Nordic Autophagy Society; 2019. p. 34. | sr |
dc.citation.spage | 34 | |
dc.type.version | publishedVersion | sr |
dc.identifier.fulltext | https://radar.ibiss.bg.ac.rs/bitstream/id/17531/bitstream_17531.pdf | |
dc.citation.rank | M34 | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_ibiss_6661 |