TY  - CONF
AU  - Jeremić, Marija
AU  - Jovanović, Maja
AU  - Tovilović-Kovačević, Gordana
AU  - Harhaji-Trajković, Ljubica
AU  - Zogović, Nevena
AU  - Vukojević, Milica
AU  - Kostić, Vladimir
AU  - Marković, Ivanka D.
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4450
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. Level of AMPK-activated pULK was reduced in
presence of CM, but pharmacological activators of AMPK
reversed that effect. Pharmacological inhibitors of autophagy,
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  - Hoboken: Wiley
C3  - FEBS OpenBio
T1  - Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy
IS  - Supplement 1
VL  - 11
SP  - 463
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4450
ER  - 

@conference{
author = "Jeremić, Marija and Jovanović, Maja and Tovilović-Kovačević, Gordana and Harhaji-Trajković, Ljubica and Zogović, Nevena and Vukojević, Milica and Kostić, Vladimir and Marković, Ivanka D. and Trajković, Vladimir",
year = "2021",
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. Level of AMPK-activated pULK was reduced in
presence of CM, but pharmacological activators of AMPK
reversed that effect. Pharmacological inhibitors of autophagy,
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 = "Hoboken: Wiley",
journal = "FEBS OpenBio",
title = "Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy",
number = "Supplement 1",
volume = "11",
pages = "463",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4450"
}

Jeremić, M., Jovanović, M., Tovilović-Kovačević, G., Harhaji-Trajković, L., Zogović, N., Vukojević, M., Kostić, V., Marković, I. D.,& Trajković, V.. (2021). Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy. in FEBS OpenBio
Hoboken: Wiley., 11(Supplement 1), 463.
https://hdl.handle.net/21.15107/rcub_ibiss_4450

Jeremić M, Jovanović M, Tovilović-Kovačević G, Harhaji-Trajković L, Zogović N, Vukojević M, Kostić V, Marković ID, Trajković V. Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy. in FEBS OpenBio. 2021;11(Supplement 1):463.
https://hdl.handle.net/21.15107/rcub_ibiss_4450 .

Jeremić, Marija, Jovanović, Maja, Tovilović-Kovačević, Gordana, Harhaji-Trajković, Ljubica, Zogović, Nevena, Vukojević, Milica, Kostić, Vladimir, Marković, Ivanka D., Trajković, Vladimir, "Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy" in FEBS OpenBio, 11, no. Supplement 1 (2021):463,
https://hdl.handle.net/21.15107/rcub_ibiss_4450 .

TY  - JOUR
AU  - Stevanović, I.D.
AU  - Jovanović, M.D.
AU  - Čolić, M.
AU  - Jelenković, A.
AU  - Mihajlović, R.
AU  - Stojanović, I.
AU  - Ninković, M.
PY  - 2010
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/270
AB  - The presented experiment was carried out to determine the effectiveness of the inducible nitric oxide synthase inhibitor - aminoguanidine in modulating the toxicity of aluminum chloride on the nitrite levels, malondialdehyde concentration, reduced glutathione content, as well as cytochrome c oxidase activity of Wistar rats. The animals were killed 3 h and 30 days after treatment and the hippocampus was removed. The biochemical results show that aluminum acts as a pro-oxidant, while aminoguanidine exerts an antioxidant action in aluminum chloride-treated animals. We have also applied immunohistochemical techniques to identify iNOS expression after the treatment. Our data suggest that aminoguanidine can be effective in the protection of toxicity induced by aluminum chloride.
AB  - U eksperimentu je određivana efikasnost inhibitora inducibilne forme azot oksid sintaze - aminogvanidina, u modulaciji toksičnosti aluminijum hlorida na nivo nitrita, koncentraciju malondialdehida, sadržaj redukovanog glutationa, kao i aktivnost citohrom c oksidaze kod Wistar pacova. Životinje su dekapitovane 3 časa i 30 dana nakon odgovarajućeg tretmana i izolovan je hipokampus. Rezultati dobijeni na biohemijskom nivou pokazuju da aluminijum deluje kao pro-oksidant, dok aminogvanidin pokazuje antioksidativno dejstvo kod životinja tretiranih aluminijum hloridom. Pored toga, korišćene su i imunohistohemijske tehnike za identifikaciju iNOS ekspresije, 3 časa nakon primene odgovarajućeg tretmana. Naši rezultati pokazuju da aminogvanidin može sprečiti toksičnost indukovanu aluminijum hloridom.
T2  - Archives of Biological Sciences
T1  - Efekat aminogvanidina, inhibitora azot oksid sintaze, na toksičnost AlCl3 u hipokampusu pacova
T1  - The effect of aminoguanidine, an inducible nitric oxide synthase inhibitor, on AlCl3 toxicity in the rat hippocampus
IS  - 4
VL  - 62
SP  - 981
EP  - 991
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_270
ER  - 

@article{
author = "Stevanović, I.D. and Jovanović, M.D. and Čolić, M. and Jelenković, A. and Mihajlović, R. and Stojanović, I. and Ninković, M.",
year = "2010, 2010",
abstract = "The presented experiment was carried out to determine the effectiveness of the inducible nitric oxide synthase inhibitor - aminoguanidine in modulating the toxicity of aluminum chloride on the nitrite levels, malondialdehyde concentration, reduced glutathione content, as well as cytochrome c oxidase activity of Wistar rats. The animals were killed 3 h and 30 days after treatment and the hippocampus was removed. The biochemical results show that aluminum acts as a pro-oxidant, while aminoguanidine exerts an antioxidant action in aluminum chloride-treated animals. We have also applied immunohistochemical techniques to identify iNOS expression after the treatment. Our data suggest that aminoguanidine can be effective in the protection of toxicity induced by aluminum chloride., U eksperimentu je određivana efikasnost inhibitora inducibilne forme azot oksid sintaze - aminogvanidina, u modulaciji toksičnosti aluminijum hlorida na nivo nitrita, koncentraciju malondialdehida, sadržaj redukovanog glutationa, kao i aktivnost citohrom c oksidaze kod Wistar pacova. Životinje su dekapitovane 3 časa i 30 dana nakon odgovarajućeg tretmana i izolovan je hipokampus. Rezultati dobijeni na biohemijskom nivou pokazuju da aluminijum deluje kao pro-oksidant, dok aminogvanidin pokazuje antioksidativno dejstvo kod životinja tretiranih aluminijum hloridom. Pored toga, korišćene su i imunohistohemijske tehnike za identifikaciju iNOS ekspresije, 3 časa nakon primene odgovarajućeg tretmana. Naši rezultati pokazuju da aminogvanidin može sprečiti toksičnost indukovanu aluminijum hloridom.",
journal = "Archives of Biological Sciences",
title = "Efekat aminogvanidina, inhibitora azot oksid sintaze, na toksičnost AlCl3 u hipokampusu pacova, The effect of aminoguanidine, an inducible nitric oxide synthase inhibitor, on AlCl3 toxicity in the rat hippocampus",
number = "4",
volume = "62",
pages = "981-991",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_270"
}

Stevanović, I.D., Jovanović, M.D., Čolić, M., Jelenković, A., Mihajlović, R., Stojanović, I.,& Ninković, M.. (2010). Efekat aminogvanidina, inhibitora azot oksid sintaze, na toksičnost AlCl3 u hipokampusu pacova. in Archives of Biological Sciences, 62(4), 981-991.
https://hdl.handle.net/21.15107/rcub_ibiss_270

Stevanović I, Jovanović M, Čolić M, Jelenković A, Mihajlović R, Stojanović I, Ninković M. Efekat aminogvanidina, inhibitora azot oksid sintaze, na toksičnost AlCl3 u hipokampusu pacova. in Archives of Biological Sciences. 2010;62(4):981-991.
https://hdl.handle.net/21.15107/rcub_ibiss_270 .

Stevanović, I.D., Jovanović, M.D., Čolić, M., Jelenković, A., Mihajlović, R., Stojanović, I., Ninković, M., "Efekat aminogvanidina, inhibitora azot oksid sintaze, na toksičnost AlCl3 u hipokampusu pacova" in Archives of Biological Sciences, 62, no. 4 (2010):981-991,
https://hdl.handle.net/21.15107/rcub_ibiss_270 .