TY  - JOUR
AU  - Mandić, Miloš
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Jovanović, Maja
AU  - Bošnjak, Mihajlo
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Ćirić, Darko
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0024320522001813
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35304128
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4947
AB  - We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.
PB  - Elsevier Inc.
T2  - Life Sciences
T1  - MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.
VL  - 297
DO  - 10.1016/j.lfs.2022.120481
SP  - 120481
ER  - 

@article{
author = "Mandić, Miloš and Misirkić Marjanović, Maja and Vučićević, Ljubica and Jovanović, Maja and Bošnjak, Mihajlo and Perović, Vladimir and Ristić, Biljana and Ćirić, Darko and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2022",
abstract = "We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.",
publisher = "Elsevier Inc.",
journal = "Life Sciences",
title = "MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.",
volume = "297",
doi = "10.1016/j.lfs.2022.120481",
pages = "120481"
}

Mandić, M., Misirkić Marjanović, M., Vučićević, L., Jovanović, M., Bošnjak, M., Perović, V., Ristić, B., Ćirić, D., Harhaji-Trajković, L.,& Trajković, V.. (2022). MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.. in Life Sciences
Elsevier Inc.., 297, 120481.
https://doi.org/10.1016/j.lfs.2022.120481

Mandić M, Misirkić Marjanović M, Vučićević L, Jovanović M, Bošnjak M, Perović V, Ristić B, Ćirić D, Harhaji-Trajković L, Trajković V. MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.. in Life Sciences. 2022;297:120481.
doi:10.1016/j.lfs.2022.120481 .

Mandić, Miloš, Misirkić Marjanović, Maja, Vučićević, Ljubica, Jovanović, Maja, Bošnjak, Mihajlo, Perović, Vladimir, Ristić, Biljana, Ćirić, Darko, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells." in Life Sciences, 297 (2022):120481,
https://doi.org/10.1016/j.lfs.2022.120481 . .

TY  - JOUR
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Ćirić, Darko
AU  - Martinović, Tamara
AU  - Jovanović, Maja
AU  - Isaković, Aleksandra
AU  - Marković, Ivanka
AU  - Šaponjić, Jasna
AU  - Foretz, Marc
AU  - Rabanal-Ruiz, Yoana
AU  - Korolchuk, Viktor I.
AU  - Trajković, Vladimir
PY  - 2020
UR  - http://link.springer.com/10.1007/s00018-019-03356-2
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3528
AB  - We investigated the role of autophagy, a controlled lysosomal degradation of cellular macromolecules and organelles, in glutamate excitotoxicity during nutrient deprivation in vitro. The incubation in low-glucose serum/amino acid-free cell culture medium synergized with glutamate in increasing AMP/ATP ratio and causing excitotoxic necrosis in SH-SY5Y human neuroblastoma cells. Glutamate suppressed starvation-triggered autophagy, as confirmed by diminished intracellular acidification, lower LC3 punctuation and LC3-I conversion to autophagosome-associated LC3-II, reduced expression of proautophagic beclin-1 and ATG5, increase of the selective autophagic target NBR1, and decreased number of autophagic vesicles. Similar results were observed in PC12 rat pheochromocytoma cells. Both glutamate-mediated excitotoxicity and autophagy inhibition in starved SH-SY5Y cells were reverted by NMDA antagonist memantine and mimicked by NMDA agonists D-aspartate and ibotenate. Glutamate reduced starvation-triggered phosphorylation of the energy sensor AMP-activated protein kinase (AMPK) without affecting the activity of mammalian target of rapamycin complex 1, a major negative regulator of autophagy. This was associated with reduced mRNA levels of autophagy transcriptional activators (FOXO3, ATF4) and molecules involved in autophagy initiation (ULK1, ATG13, FIP200), autophagosome nucleation/elongation (ATG14, beclin-1, ATG5), and autophagic cargo delivery to autophagosomes (SQSTM1). Glutamate-mediated transcriptional repression of autophagy was alleviated by overexpression of constitutively active AMPK. Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, as well as genetic or pharmacological autophagy induction by TFEB overexpression or lithium chloride, reduced the sensitivity of nutrient-deprived SH-SY5Y cells to glutamate excitotoxicity. These data indicate that transcriptional inhibition of AMPK-dependent cytoprotective autophagy is involved in glutamate-mediated excitotoxicity during nutrient deprivation in vitro.
T2  - Cellular and Molecular Life Sciences
T1  - Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells.
VL  - 77
DO  - 10.1007/s00018-019-03356-2
SP  - 3383
EP  - 3399
ER  - 

@article{
author = "Vučićević, Ljubica and Misirkić Marjanović, Maja and Ćirić, Darko and Martinović, Tamara and Jovanović, Maja and Isaković, Aleksandra and Marković, Ivanka and Šaponjić, Jasna and Foretz, Marc and Rabanal-Ruiz, Yoana and Korolchuk, Viktor I. and Trajković, Vladimir",
year = "2020",
abstract = "We investigated the role of autophagy, a controlled lysosomal degradation of cellular macromolecules and organelles, in glutamate excitotoxicity during nutrient deprivation in vitro. The incubation in low-glucose serum/amino acid-free cell culture medium synergized with glutamate in increasing AMP/ATP ratio and causing excitotoxic necrosis in SH-SY5Y human neuroblastoma cells. Glutamate suppressed starvation-triggered autophagy, as confirmed by diminished intracellular acidification, lower LC3 punctuation and LC3-I conversion to autophagosome-associated LC3-II, reduced expression of proautophagic beclin-1 and ATG5, increase of the selective autophagic target NBR1, and decreased number of autophagic vesicles. Similar results were observed in PC12 rat pheochromocytoma cells. Both glutamate-mediated excitotoxicity and autophagy inhibition in starved SH-SY5Y cells were reverted by NMDA antagonist memantine and mimicked by NMDA agonists D-aspartate and ibotenate. Glutamate reduced starvation-triggered phosphorylation of the energy sensor AMP-activated protein kinase (AMPK) without affecting the activity of mammalian target of rapamycin complex 1, a major negative regulator of autophagy. This was associated with reduced mRNA levels of autophagy transcriptional activators (FOXO3, ATF4) and molecules involved in autophagy initiation (ULK1, ATG13, FIP200), autophagosome nucleation/elongation (ATG14, beclin-1, ATG5), and autophagic cargo delivery to autophagosomes (SQSTM1). Glutamate-mediated transcriptional repression of autophagy was alleviated by overexpression of constitutively active AMPK. Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, as well as genetic or pharmacological autophagy induction by TFEB overexpression or lithium chloride, reduced the sensitivity of nutrient-deprived SH-SY5Y cells to glutamate excitotoxicity. These data indicate that transcriptional inhibition of AMPK-dependent cytoprotective autophagy is involved in glutamate-mediated excitotoxicity during nutrient deprivation in vitro.",
journal = "Cellular and Molecular Life Sciences",
title = "Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells.",
volume = "77",
doi = "10.1007/s00018-019-03356-2",
pages = "3383-3399"
}

Vučićević, L., Misirkić Marjanović, M., Ćirić, D., Martinović, T., Jovanović, M., Isaković, A., Marković, I., Šaponjić, J., Foretz, M., Rabanal-Ruiz, Y., Korolchuk, V. I.,& Trajković, V.. (2020). Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells.. in Cellular and Molecular Life Sciences, 77, 3383-3399.
https://doi.org/10.1007/s00018-019-03356-2

Vučićević L, Misirkić Marjanović M, Ćirić D, Martinović T, Jovanović M, Isaković A, Marković I, Šaponjić J, Foretz M, Rabanal-Ruiz Y, Korolchuk VI, Trajković V. Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells.. in Cellular and Molecular Life Sciences. 2020;77:3383-3399.
doi:10.1007/s00018-019-03356-2 .

Vučićević, Ljubica, Misirkić Marjanović, Maja, Ćirić, Darko, Martinović, Tamara, Jovanović, Maja, Isaković, Aleksandra, Marković, Ivanka, Šaponjić, Jasna, Foretz, Marc, Rabanal-Ruiz, Yoana, Korolchuk, Viktor I., Trajković, Vladimir, "Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells." in Cellular and Molecular Life Sciences, 77 (2020):3383-3399,
https://doi.org/10.1007/s00018-019-03356-2 . .

TY  - CONF
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Ćirić, Darko
AU  - Martinović, Tamara
AU  - Jovanović, Maja
AU  - Isaković, Aleksandra
AU  - Marković, Ivanka
AU  - Trajković, Vladimir
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6661
AB  - 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.
PB  - Nordic Autophagy Society
C3  - 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Nederlands
T1  - Glutamate-mediated autophagy inhibition intensifies excitotoxic death of nutrient-deprived SH-SY5Y neuroblastoma cells
SP  - 34
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6661
ER  - 

@conference{
author = "Misirkić Marjanović, Maja and Vučićević, Ljubica and Ćirić, Darko and Martinović, Tamara and Jovanović, Maja and Isaković, Aleksandra and Marković, Ivanka and Trajković, Vladimir",
year = "2019",
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.",
publisher = "Nordic Autophagy Society",
journal = "3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Nederlands",
title = "Glutamate-mediated autophagy inhibition intensifies excitotoxic death of nutrient-deprived SH-SY5Y neuroblastoma cells",
pages = "34",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6661"
}

Misirkić Marjanović, M., Vučićević, L., Ćirić, D., Martinović, T., Jovanović, M., Isaković, A., Marković, I.,& Trajković, V.. (2019). Glutamate-mediated autophagy inhibition intensifies excitotoxic death of nutrient-deprived SH-SY5Y neuroblastoma cells. in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Nederlands
Nordic Autophagy Society., 34.
https://hdl.handle.net/21.15107/rcub_ibiss_6661

Misirkić Marjanović M, Vučićević L, Ćirić D, Martinović T, Jovanović M, Isaković A, Marković I, Trajković V. Glutamate-mediated autophagy inhibition intensifies excitotoxic death of nutrient-deprived SH-SY5Y neuroblastoma cells. in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Nederlands. 2019;:34.
https://hdl.handle.net/21.15107/rcub_ibiss_6661 .

Misirkić Marjanović, Maja, Vučićević, Ljubica, Ćirić, Darko, Martinović, Tamara, Jovanović, Maja, Isaković, Aleksandra, Marković, Ivanka, Trajković, Vladimir, "Glutamate-mediated autophagy inhibition intensifies excitotoxic death of nutrient-deprived SH-SY5Y neuroblastoma cells" in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Nederlands (2019):34,
https://hdl.handle.net/21.15107/rcub_ibiss_6661 .

TY  - CONF
AU  - Mandić, Miloš
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Jovanović, Maja
AU  - Bošnjak, Mihajlo
AU  - Perović, Vladimir
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2019
UR  - https://nordicautophagy.org
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6597
AB  - We investigated the mechanism and the role of autophagy in phorbol myristate acetate (PMA)-induced myeloid differentiation of human acute myeloid leukemia HL-60 cells. Methods: The mRNA levels of myeloid differentiation markers colony stimulating factor 1 receptor (CSF1R), early growth response protein 1 (EGR1), and interleukin 8 (IL-8), were assessed by real-time RT-PCR. Cell cycle arrest and the expression of surface myeloid marker CD11b were analyzed by flow cytometry. Autophagy was monitored by acridine orange staining, RT-PCR analysis of autophagy-related (ATG) gene expression, LC3-II/p62 immunoblotting, Beclin-1/Bcl-2 interaction, nuclear translocation of transcription factor EB (TFEB). The activation of MAP kinases extracelluar signal-regulated kinase (ERK) and c-Jun-N terminal kinase (JNK) was assessed by immunoblotting. Pharmacological inhibition and RNA interference (RNAi) were used to determine the role of MAP kinases in autophagy and HL60 cell differentiation, while the role of autophagy in HL60 differentiation was analyzed using RNAi-mediated knockdown of ATG5 and p62. Results: PMA-induced differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of p21, CD11b, CSF1R, EGR1, and IL-8. The induction of autophagy was demonstrated by accumulation of LC3-II, the increase in autophagic flux, the increase in expression of ATG genes, nuclear translocation of TFEB and dissociation of Beclin1from Bcl-2.The suppression of autophagy by RNAi–mediated knockdown of ATG5 or p62 counteracted myeloid differentiation of HL60 cells. Both ERK and JNK were activated by PMA, and their pharmacological and genetic inhibition decreased PMA-induced autophagy and differentiation of HL60 cells. Conclusion: Our study revealed the involvement of JNK and ERK in autophagy-dependent myeloid differentiation of HL60 cells, indicating MAP kinase-mediated autophagy as a possible target for treatment of acute myeloid leukemia
PB  - Nordic Autophagy Society
C3  - 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands
T1  - MAP kinase-dependent autophagy is involved in phorbol myristate acetate differentiation of HL-60 leukemia cells
SP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6597
ER  - 

@conference{
author = "Mandić, Miloš and Misirkić Marjanović, Maja and Vučićević, Ljubica and Jovanović, Maja and Bošnjak, Mihajlo and Perović, Vladimir and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2019",
abstract = "We investigated the mechanism and the role of autophagy in phorbol myristate acetate (PMA)-induced myeloid differentiation of human acute myeloid leukemia HL-60 cells. Methods: The mRNA levels of myeloid differentiation markers colony stimulating factor 1 receptor (CSF1R), early growth response protein 1 (EGR1), and interleukin 8 (IL-8), were assessed by real-time RT-PCR. Cell cycle arrest and the expression of surface myeloid marker CD11b were analyzed by flow cytometry. Autophagy was monitored by acridine orange staining, RT-PCR analysis of autophagy-related (ATG) gene expression, LC3-II/p62 immunoblotting, Beclin-1/Bcl-2 interaction, nuclear translocation of transcription factor EB (TFEB). The activation of MAP kinases extracelluar signal-regulated kinase (ERK) and c-Jun-N terminal kinase (JNK) was assessed by immunoblotting. Pharmacological inhibition and RNA interference (RNAi) were used to determine the role of MAP kinases in autophagy and HL60 cell differentiation, while the role of autophagy in HL60 differentiation was analyzed using RNAi-mediated knockdown of ATG5 and p62. Results: PMA-induced differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of p21, CD11b, CSF1R, EGR1, and IL-8. The induction of autophagy was demonstrated by accumulation of LC3-II, the increase in autophagic flux, the increase in expression of ATG genes, nuclear translocation of TFEB and dissociation of Beclin1from Bcl-2.The suppression of autophagy by RNAi–mediated knockdown of ATG5 or p62 counteracted myeloid differentiation of HL60 cells. Both ERK and JNK were activated by PMA, and their pharmacological and genetic inhibition decreased PMA-induced autophagy and differentiation of HL60 cells. Conclusion: Our study revealed the involvement of JNK and ERK in autophagy-dependent myeloid differentiation of HL60 cells, indicating MAP kinase-mediated autophagy as a possible target for treatment of acute myeloid leukemia",
publisher = "Nordic Autophagy Society",
journal = "3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands",
title = "MAP kinase-dependent autophagy is involved in phorbol myristate acetate differentiation of HL-60 leukemia cells",
pages = "33",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6597"
}

Mandić, M., Misirkić Marjanović, M., Vučićević, L., Jovanović, M., Bošnjak, M., Perović, V., Harhaji-Trajković, L.,& Trajković, V.. (2019). MAP kinase-dependent autophagy is involved in phorbol myristate acetate differentiation of HL-60 leukemia cells. in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands
Nordic Autophagy Society., 33.
https://hdl.handle.net/21.15107/rcub_ibiss_6597

Mandić M, Misirkić Marjanović M, Vučićević L, Jovanović M, Bošnjak M, Perović V, Harhaji-Trajković L, Trajković V. MAP kinase-dependent autophagy is involved in phorbol myristate acetate differentiation of HL-60 leukemia cells. in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands. 2019;:33.
https://hdl.handle.net/21.15107/rcub_ibiss_6597 .

Mandić, Miloš, Misirkić Marjanović, Maja, Vučićević, Ljubica, Jovanović, Maja, Bošnjak, Mihajlo, Perović, Vladimir, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "MAP kinase-dependent autophagy is involved in phorbol myristate acetate differentiation of HL-60 leukemia cells" in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands (2019):33,
https://hdl.handle.net/21.15107/rcub_ibiss_6597 .

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 .

TY  - CONF
AU  - Jeremić, Marija
AU  - Jovanović, Maja
AU  - Dulović, Marija
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Harhaji-Trajković, Ljubica
AU  - Vukojević, Milica
AU  - Kostić, Vladimir
AU  - Marković, Ivanka
AU  - Trajković, Vladimir
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6342
AB  - Alpha-synuclein (ASYN) is regarded as one of the key culprits in pathogenesis of synucleinopathies, including Parkinson’s disease, and impaired regulation of autophagy is associated with the ASYN aggregation. Autophagy is regulated by complex mechanisms, including AMP activated protein kinase (AMPK), a key energy sensor regulating cellular metabolism to maintain energy homeostasis. The aim of our study was to investigate the role of AMPK and autophagy in neurotoxic effect of secreted ASYN, as well as dopamine-modified and nitrated recombinant wild-type ASYN oligomers, on retinoic acid (RA)-differentiated SH-SY5Y cells. The culture supernatant from neuroblastoma cells stably expressing wt ASYN was collected and used as conditioned medium (CM). The presence of wt ASYN in CM was confirmed by immunoblot, following lyophilisation. The CM, as well as recombinant dopamine-modified or nitrated ASYN, all reduced viability in differentiated SH-SY5Y cells. This decrease in viability was accompanied by reduced AMPK activation, increased conversion of LC3-I to LC3-II and increase
in Beclin-1 level, as demonstrated by immunoblot. Pharmacological activators of AMPK and autophagy (metformin and AICAR) significantly increased the cells’ viability in the presence of CM and modified ASYN forms. Pharmacological inhibitors of autophagy (chloroqine, bafilomycin A1 and ammonium-chloride), further reduced cell viability in the presence of extracellular ASYN. The shRNA-mediated LC3 downregulation, as well as the RNA interference-mediated knockdown of ATG7 gene, both important for autophagosome biogenesis/maturation, increased sensitivity of SH-SY5Y cells to the extracellular ASYN-induced toxicity. These data demonstrate the protective role of AMPK and autophagy against the toxicity of extracellular ASYN, suggesting that their modulation may be a promising neuroprotective strategy in Parkinson’s disease.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - The protective role of AMPK and autophagy in neurotoxicity caused by extracellular alpha-synuclein
SP  - 493
EP  - 493
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6342
ER  - 

@conference{
author = "Jeremić, Marija and Jovanović, Maja and Dulović, Marija and Tovilović-Kovačević, Gordana and Zogović, Nevena and Harhaji-Trajković, Ljubica and Vukojević, Milica and Kostić, Vladimir and Marković, Ivanka and Trajković, Vladimir",
year = "2019",
abstract = "Alpha-synuclein (ASYN) is regarded as one of the key culprits in pathogenesis of synucleinopathies, including Parkinson’s disease, and impaired regulation of autophagy is associated with the ASYN aggregation. Autophagy is regulated by complex mechanisms, including AMP activated protein kinase (AMPK), a key energy sensor regulating cellular metabolism to maintain energy homeostasis. The aim of our study was to investigate the role of AMPK and autophagy in neurotoxic effect of secreted ASYN, as well as dopamine-modified and nitrated recombinant wild-type ASYN oligomers, on retinoic acid (RA)-differentiated SH-SY5Y cells. The culture supernatant from neuroblastoma cells stably expressing wt ASYN was collected and used as conditioned medium (CM). The presence of wt ASYN in CM was confirmed by immunoblot, following lyophilisation. The CM, as well as recombinant dopamine-modified or nitrated ASYN, all reduced viability in differentiated SH-SY5Y cells. This decrease in viability was accompanied by reduced AMPK activation, increased conversion of LC3-I to LC3-II and increase
in Beclin-1 level, as demonstrated by immunoblot. Pharmacological activators of AMPK and autophagy (metformin and AICAR) significantly increased the cells’ viability in the presence of CM and modified ASYN forms. Pharmacological inhibitors of autophagy (chloroqine, bafilomycin A1 and ammonium-chloride), further reduced cell viability in the presence of extracellular ASYN. The shRNA-mediated LC3 downregulation, as well as the RNA interference-mediated knockdown of ATG7 gene, both important for autophagosome biogenesis/maturation, increased sensitivity of SH-SY5Y cells to the extracellular ASYN-induced toxicity. These data demonstrate the protective role of AMPK and autophagy against the toxicity of extracellular ASYN, suggesting that their modulation may be a promising neuroprotective strategy in Parkinson’s disease.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "The protective role of AMPK and autophagy in neurotoxicity caused by extracellular alpha-synuclein",
pages = "493-493",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6342"
}

Jeremić, M., Jovanović, M., Dulović, M., Tovilović-Kovačević, G., Zogović, N., Harhaji-Trajković, L., Vukojević, M., Kostić, V., Marković, I.,& Trajković, V.. (2019). The protective role of AMPK and autophagy in neurotoxicity caused by extracellular alpha-synuclein. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 493-493.
https://hdl.handle.net/21.15107/rcub_ibiss_6342

Jeremić M, Jovanović M, Dulović M, Tovilović-Kovačević G, Zogović N, Harhaji-Trajković L, Vukojević M, Kostić V, Marković I, Trajković V. The protective role of AMPK and autophagy in neurotoxicity caused by extracellular alpha-synuclein. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:493-493.
https://hdl.handle.net/21.15107/rcub_ibiss_6342 .

Jeremić, Marija, Jovanović, Maja, Dulović, Marija, Tovilović-Kovačević, Gordana, Zogović, Nevena, Harhaji-Trajković, Ljubica, Vukojević, Milica, Kostić, Vladimir, Marković, Ivanka, Trajković, Vladimir, "The protective role of AMPK and autophagy in neurotoxicity caused by extracellular alpha-synuclein" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):493-493,
https://hdl.handle.net/21.15107/rcub_ibiss_6342 .

TY  - CONF
AU  - Mandić, Miloš
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Jovanović, Maja
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6287
AB  - Introduction: Phorbol myristate acetate (PMA) is in
clinical investigation for treatment of acute myeloid
leukemia due to its differentiating ability. Cell differentiation could be accompanied by senescence, a state
of irreversible cell cycle arrest.
Our aim was to investigate the ability of PMA to initiate
senescence in HL60 human leukemia cells.
Methods: Cell morphology was analyzed using phase
contrast microscopy. Cell cycle arrest was assessed
by flow cytometric analysis of propidium iodide stained
cells and BrdU colorimetric assay. Activity of senescence-associated beta-galactosidase (SA-βgal) was
assessed by cytochemical staining and flow cytometric analysis of fluorescein di-β-D-galactopyranoside
(FDG) stained cells. Senescence-associated gene expression of: cell cycle inhibitor p21, interleukin-8 (IL-8),
lamin B1 were quantified by RT-PCR, while activation
of NF-κB, main regulator of senescence associated secretory phenotype, was examined by immunoblotting.
Results: After the PMA treatment HL60 were enlarged and flattened with cytoplasmic vacuoles resembling morphology of senescent cells. Block in
leukemia cell proliferation in G1 phase was accompanied with increase in expression of cell cycle inhibitor p21 in PMA treated cells. Finally, PMA stimulated
SA-βgal activity, expression of genes responsible for
senescence associated secretory phenotype, NF-κB
and IL-8, while downregulating Lamin B1 expression.
Conclusion: Our results suggest that in addition to
PMA-induced cellular differentiation, senescence
participates in its previously shown cytostatic effect,
further supporting its investigation as a potential antileukemic drug.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade
C3  - Program & Book of Abstracts. IUBMB Advanced School Nutrition, Metabolism and Aging; 2018 Oct 15-19; Petnica, Serbia
T1  - Phorbol 12-myristate 13-acetate induces senescence of HL-60 leukemic cells
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6287
ER  - 

@conference{
author = "Mandić, Miloš and Vučićević, Ljubica and Misirkić Marjanović, Maja and Jovanović, Maja and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2018",
abstract = "Introduction: Phorbol myristate acetate (PMA) is in
clinical investigation for treatment of acute myeloid
leukemia due to its differentiating ability. Cell differentiation could be accompanied by senescence, a state
of irreversible cell cycle arrest.
Our aim was to investigate the ability of PMA to initiate
senescence in HL60 human leukemia cells.
Methods: Cell morphology was analyzed using phase
contrast microscopy. Cell cycle arrest was assessed
by flow cytometric analysis of propidium iodide stained
cells and BrdU colorimetric assay. Activity of senescence-associated beta-galactosidase (SA-βgal) was
assessed by cytochemical staining and flow cytometric analysis of fluorescein di-β-D-galactopyranoside
(FDG) stained cells. Senescence-associated gene expression of: cell cycle inhibitor p21, interleukin-8 (IL-8),
lamin B1 were quantified by RT-PCR, while activation
of NF-κB, main regulator of senescence associated secretory phenotype, was examined by immunoblotting.
Results: After the PMA treatment HL60 were enlarged and flattened with cytoplasmic vacuoles resembling morphology of senescent cells. Block in
leukemia cell proliferation in G1 phase was accompanied with increase in expression of cell cycle inhibitor p21 in PMA treated cells. Finally, PMA stimulated
SA-βgal activity, expression of genes responsible for
senescence associated secretory phenotype, NF-κB
and IL-8, while downregulating Lamin B1 expression.
Conclusion: Our results suggest that in addition to
PMA-induced cellular differentiation, senescence
participates in its previously shown cytostatic effect,
further supporting its investigation as a potential antileukemic drug.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade",
journal = "Program & Book of Abstracts. IUBMB Advanced School Nutrition, Metabolism and Aging; 2018 Oct 15-19; Petnica, Serbia",
title = "Phorbol 12-myristate 13-acetate induces senescence of HL-60 leukemic cells",
pages = "38",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6287"
}

Mandić, M., Vučićević, L., Misirkić Marjanović, M., Jovanović, M., Harhaji-Trajković, L.,& Trajković, V.. (2018). Phorbol 12-myristate 13-acetate induces senescence of HL-60 leukemic cells. in Program & Book of Abstracts. IUBMB Advanced School Nutrition, Metabolism and Aging; 2018 Oct 15-19; Petnica, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade., 38.
https://hdl.handle.net/21.15107/rcub_ibiss_6287

Mandić M, Vučićević L, Misirkić Marjanović M, Jovanović M, Harhaji-Trajković L, Trajković V. Phorbol 12-myristate 13-acetate induces senescence of HL-60 leukemic cells. in Program & Book of Abstracts. IUBMB Advanced School Nutrition, Metabolism and Aging; 2018 Oct 15-19; Petnica, Serbia. 2018;:38.
https://hdl.handle.net/21.15107/rcub_ibiss_6287 .

Mandić, Miloš, Vučićević, Ljubica, Misirkić Marjanović, Maja, Jovanović, Maja, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Phorbol 12-myristate 13-acetate induces senescence of HL-60 leukemic cells" in Program & Book of Abstracts. IUBMB Advanced School Nutrition, Metabolism and Aging; 2018 Oct 15-19; Petnica, Serbia (2018):38,
https://hdl.handle.net/21.15107/rcub_ibiss_6287 .

TY  - JOUR
AU  - Arsikin-Csordas, Katarina
AU  - Kravić-Stevović, Tamara
AU  - Jovanović, Maja
AU  - Ristić, Biljana
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Bumbaširević, Vladimir
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2012
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6366
AB  - The role of the main intracellular energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK) in the induction of autophagic response and cell death was investigated in SH-SY5Y human neuroblastoma cells exposed to the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). The induction of autophagy in SH-SY5Y cells was demonstrated by acridine orange staining of intracellular acidic vesicles, the presence of autophagosome- and autophagolysosome-like vesicles confirmed by transmission electron microscopy, as well as by microtubule-associated protein 1 light-chain 3 (LC3) conversion and p62 degradation detected by immunoblotting. 6-OHDA induced phosphorylation of AMPK and its target Raptor, followed by the dephosphorylation of the major autophagy inhibitor mammalian target of rapamycin (mTOR) and its substrate p70S6 kinase (S6K). 6-OHDA treatment failed to suppress mTOR/S6K phosphorylation and to increase LC3 conversion, p62 degradation and cytoplasmatic acidification in neuroblastoma cells in which AMPK expression was downregulated by RNA interference. Transfection of SH-SY5Y cells with AMPK or LC3β shRNA, as well as treatment with pharmacological autophagy inhibitors suppressed, while mTOR inhibitor rapamycin potentiated 6-OHDA-induced oxidative stress and apoptotic cell death. 6-OHDA induced phosphorylation of p38 mitogen-activated protein (MAP) kinase in an AMPK-dependent manner, and pharmacological inhibition of p38 MAP kinase reduced neurotoxicity, but not AMPK activation and autophagy triggered by 6-OHDA. Finally, the antioxidant N-acetyl cysteine antagonized 6-OHDA-induced activation of AMPK, p38 and autophagy. These data suggest that oxidative stress-mediated AMPK/mTOR-dependent autophagy and AMPK/p38-dependent apoptosis could be valid therapeutic targets for neuroprotection.
PB  - Amsterdam: Elsevier
T2  - Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
T1  - Autophagy-dependent and -independent involvement of AMP-activated protein kinase in 6-hydroxydopamine toxicity to SH-SY5Y neuroblastoma cells
IS  - 11
VL  - 1822
DO  - 10.1016/j.bbadis.2012.08.006.
SP  - 1826
EP  - 1836
ER  - 

@article{
author = "Arsikin-Csordas, Katarina and Kravić-Stevović, Tamara and Jovanović, Maja and Ristić, Biljana and Tovilović-Kovačević, Gordana and Zogović, Nevena and Bumbaširević, Vladimir and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2012",
abstract = "The role of the main intracellular energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK) in the induction of autophagic response and cell death was investigated in SH-SY5Y human neuroblastoma cells exposed to the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). The induction of autophagy in SH-SY5Y cells was demonstrated by acridine orange staining of intracellular acidic vesicles, the presence of autophagosome- and autophagolysosome-like vesicles confirmed by transmission electron microscopy, as well as by microtubule-associated protein 1 light-chain 3 (LC3) conversion and p62 degradation detected by immunoblotting. 6-OHDA induced phosphorylation of AMPK and its target Raptor, followed by the dephosphorylation of the major autophagy inhibitor mammalian target of rapamycin (mTOR) and its substrate p70S6 kinase (S6K). 6-OHDA treatment failed to suppress mTOR/S6K phosphorylation and to increase LC3 conversion, p62 degradation and cytoplasmatic acidification in neuroblastoma cells in which AMPK expression was downregulated by RNA interference. Transfection of SH-SY5Y cells with AMPK or LC3β shRNA, as well as treatment with pharmacological autophagy inhibitors suppressed, while mTOR inhibitor rapamycin potentiated 6-OHDA-induced oxidative stress and apoptotic cell death. 6-OHDA induced phosphorylation of p38 mitogen-activated protein (MAP) kinase in an AMPK-dependent manner, and pharmacological inhibition of p38 MAP kinase reduced neurotoxicity, but not AMPK activation and autophagy triggered by 6-OHDA. Finally, the antioxidant N-acetyl cysteine antagonized 6-OHDA-induced activation of AMPK, p38 and autophagy. These data suggest that oxidative stress-mediated AMPK/mTOR-dependent autophagy and AMPK/p38-dependent apoptosis could be valid therapeutic targets for neuroprotection.",
publisher = "Amsterdam: Elsevier",
journal = "Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease",
title = "Autophagy-dependent and -independent involvement of AMP-activated protein kinase in 6-hydroxydopamine toxicity to SH-SY5Y neuroblastoma cells",
number = "11",
volume = "1822",
doi = "10.1016/j.bbadis.2012.08.006.",
pages = "1826-1836"
}

Arsikin-Csordas, K., Kravić-Stevović, T., Jovanović, M., Ristić, B., Tovilović-Kovačević, G., Zogović, N., Bumbaširević, V., Trajković, V.,& Harhaji-Trajković, L.. (2012). Autophagy-dependent and -independent involvement of AMP-activated protein kinase in 6-hydroxydopamine toxicity to SH-SY5Y neuroblastoma cells. in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Amsterdam: Elsevier., 1822(11), 1826-1836.
https://doi.org/10.1016/j.bbadis.2012.08.006.

Arsikin-Csordas K, Kravić-Stevović T, Jovanović M, Ristić B, Tovilović-Kovačević G, Zogović N, Bumbaširević V, Trajković V, Harhaji-Trajković L. Autophagy-dependent and -independent involvement of AMP-activated protein kinase in 6-hydroxydopamine toxicity to SH-SY5Y neuroblastoma cells. in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2012;1822(11):1826-1836.
doi:10.1016/j.bbadis.2012.08.006. .

Arsikin-Csordas, Katarina, Kravić-Stevović, Tamara, Jovanović, Maja, Ristić, Biljana, Tovilović-Kovačević, Gordana, Zogović, Nevena, Bumbaširević, Vladimir, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Autophagy-dependent and -independent involvement of AMP-activated protein kinase in 6-hydroxydopamine toxicity to SH-SY5Y neuroblastoma cells" in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1822, no. 11 (2012):1826-1836,
https://doi.org/10.1016/j.bbadis.2012.08.006. . .