TY  - JOUR
AU  - Dragić, Milorad
AU  - Milićević, Katarina
AU  - Adžić, Marija
AU  - Stevanović, Ivana
AU  - Ninković, Milica
AU  - Grković, Ivana
AU  - Anđus, Pavle
AU  - Nedeljković, Nadežda
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9174
AB  - Astrocytes are the first responders to noxious stimuli by undergoing cellular and functional transition referred as reactive gliosis. Every acute or chronic disorder is accompanied by reactive gliosis, which could be categorized as detrimental (A1) of beneficial (A2) for nervous tissue. Another signature of pathological astrocyte activation is disturbed Ca2+ homeostasis, a common denominator of neurodegenerative diseases. Deregulation of Ca+ signaling further contributes to production of pro-inflammatory cytokines and reactive oxygen species. Trimethyltin (TMT) intoxication is a widely used model of hippocampal degeneration, sharing behavioral and molecular hallmarks of Alzheimer’s disease (AD), thus representing a useful model of AD-like pathology. However, the role of astrocyte in the etiopathology of TMT-induced degeneration as well as in AD is not fully understood. In an effort to elucidate the role of astrocytes in such pathological processes, we examined in vitro effects of TMT on primary cortical astrocytes. The application of a range of TMT concentrations (5, 10, 50, and 100 μM) revealed changes in [Ca2+]i in a dose-dependent manner. Specifically, TMT-induced Ca2+ transients were due to L-type voltage-gated calcium channels (VGCC). Additionally, TMT induced mitochondrial depolarization independent of extracellular Ca2+ and disturbed antioxidative defense of astrocyte in several time points (4, 6, and 24 h) after 10 μM TMT intoxication, inducing oxidative and nitrosative stress. Chronic exposure (24 h) to 10 μM TMT induced strong upregulation of main pro-inflammatory factors, components of signaling pathways in astrocyte activation, A1 markers, and VGCC. Taken together, our results provide an insight into cellular and molecular events of astrocyte activation in chronic neuroinflammation. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
T2  - Molecular Neurobiology
T1  - Trimethyltin Increases Intracellular Ca2+ Via L-Type Voltage-Gated Calcium Channels and Promotes Inflammatory Phenotype in Rat Astrocytes In Vitro
VL  - 58
IS  - 4
SP  - 1792
EP  - 1805
DO  - 10.1007/s12035-020-02273-x
ER  - 

@article{
author = "Dragić, Milorad and Milićević, Katarina and Adžić, Marija and Stevanović, Ivana and Ninković, Milica and Grković, Ivana and Anđus, Pavle and Nedeljković, Nadežda",
year = "2021",
abstract = "Astrocytes are the first responders to noxious stimuli by undergoing cellular and functional transition referred as reactive gliosis. Every acute or chronic disorder is accompanied by reactive gliosis, which could be categorized as detrimental (A1) of beneficial (A2) for nervous tissue. Another signature of pathological astrocyte activation is disturbed Ca2+ homeostasis, a common denominator of neurodegenerative diseases. Deregulation of Ca+ signaling further contributes to production of pro-inflammatory cytokines and reactive oxygen species. Trimethyltin (TMT) intoxication is a widely used model of hippocampal degeneration, sharing behavioral and molecular hallmarks of Alzheimer’s disease (AD), thus representing a useful model of AD-like pathology. However, the role of astrocyte in the etiopathology of TMT-induced degeneration as well as in AD is not fully understood. In an effort to elucidate the role of astrocytes in such pathological processes, we examined in vitro effects of TMT on primary cortical astrocytes. The application of a range of TMT concentrations (5, 10, 50, and 100 μM) revealed changes in [Ca2+]i in a dose-dependent manner. Specifically, TMT-induced Ca2+ transients were due to L-type voltage-gated calcium channels (VGCC). Additionally, TMT induced mitochondrial depolarization independent of extracellular Ca2+ and disturbed antioxidative defense of astrocyte in several time points (4, 6, and 24 h) after 10 μM TMT intoxication, inducing oxidative and nitrosative stress. Chronic exposure (24 h) to 10 μM TMT induced strong upregulation of main pro-inflammatory factors, components of signaling pathways in astrocyte activation, A1 markers, and VGCC. Taken together, our results provide an insight into cellular and molecular events of astrocyte activation in chronic neuroinflammation. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.",
journal = "Molecular Neurobiology",
title = "Trimethyltin Increases Intracellular Ca2+ Via L-Type Voltage-Gated Calcium Channels and Promotes Inflammatory Phenotype in Rat Astrocytes In Vitro",
volume = "58",
number = "4",
pages = "1792-1805",
doi = "10.1007/s12035-020-02273-x"
}

Dragić, M., Milićević, K., Adžić, M., Stevanović, I., Ninković, M., Grković, I., Anđus, P.,& Nedeljković, N.. (2021). Trimethyltin Increases Intracellular Ca2+ Via L-Type Voltage-Gated Calcium Channels and Promotes Inflammatory Phenotype in Rat Astrocytes In Vitro. in Molecular Neurobiology, 58(4), 1792-1805.
https://doi.org/10.1007/s12035-020-02273-x

Dragić M, Milićević K, Adžić M, Stevanović I, Ninković M, Grković I, Anđus P, Nedeljković N. Trimethyltin Increases Intracellular Ca2+ Via L-Type Voltage-Gated Calcium Channels and Promotes Inflammatory Phenotype in Rat Astrocytes In Vitro. in Molecular Neurobiology. 2021;58(4):1792-1805.
doi:10.1007/s12035-020-02273-x .

Dragić, Milorad, Milićević, Katarina, Adžić, Marija, Stevanović, Ivana, Ninković, Milica, Grković, Ivana, Anđus, Pavle, Nedeljković, Nadežda, "Trimethyltin Increases Intracellular Ca2+ Via L-Type Voltage-Gated Calcium Channels and Promotes Inflammatory Phenotype in Rat Astrocytes In Vitro" in Molecular Neurobiology, 58, no. 4 (2021):1792-1805,
https://doi.org/10.1007/s12035-020-02273-x . .

TY  - JOUR
AU  - Ganesan, Minu Karthika
AU  - Jovanović, Miloš
AU  - Šećerov, Bojana Lj.
AU  - Ignjatović, Marija
AU  - Bilban, Martin
AU  - Anđus, Pavle R.
AU  - El Refaei, Amal
AU  - Jung, Gangsoo
AU  - Li, Lin
AU  - Sase, Ajinkya
AU  - Chen, Weiqiang
AU  - Bačić, Goran
AU  - Lubec, Gert
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/133
T2  - Amino Acids
T1  - Erratum to: Radiation protection from whole-body gamma irradiation (6.7 Gy): behavioural effects and brain protein-level changes by an aminothiol compound GL2011 in the Wistar rat (vol 46, pg 1681, 2014)
VL  - 46
IS  - 10
SP  - 2445
EP  - 2445
DO  - 10.1007/s00726-014-1791-2
ER  - 

@article{
author = "Ganesan, Minu Karthika and Jovanović, Miloš and Šećerov, Bojana Lj. and Ignjatović, Marija and Bilban, Martin and Anđus, Pavle R. and El Refaei, Amal and Jung, Gangsoo and Li, Lin and Sase, Ajinkya and Chen, Weiqiang and Bačić, Goran and Lubec, Gert",
year = "2014",
journal = "Amino Acids",
title = "Erratum to: Radiation protection from whole-body gamma irradiation (6.7 Gy): behavioural effects and brain protein-level changes by an aminothiol compound GL2011 in the Wistar rat (vol 46, pg 1681, 2014)",
volume = "46",
number = "10",
pages = "2445-2445",
doi = "10.1007/s00726-014-1791-2"
}

Ganesan, M. K., Jovanović, M., Šećerov, B. Lj., Ignjatović, M., Bilban, M., Anđus, P. R., El Refaei, A., Jung, G., Li, L., Sase, A., Chen, W., Bačić, G.,& Lubec, G.. (2014). Erratum to: Radiation protection from whole-body gamma irradiation (6.7 Gy): behavioural effects and brain protein-level changes by an aminothiol compound GL2011 in the Wistar rat (vol 46, pg 1681, 2014). in Amino Acids, 46(10), 2445-2445.
https://doi.org/10.1007/s00726-014-1791-2

Ganesan MK, Jovanović M, Šećerov BL, Ignjatović M, Bilban M, Anđus PR, El Refaei A, Jung G, Li L, Sase A, Chen W, Bačić G, Lubec G. Erratum to: Radiation protection from whole-body gamma irradiation (6.7 Gy): behavioural effects and brain protein-level changes by an aminothiol compound GL2011 in the Wistar rat (vol 46, pg 1681, 2014). in Amino Acids. 2014;46(10):2445-2445.
doi:10.1007/s00726-014-1791-2 .

Ganesan, Minu Karthika, Jovanović, Miloš, Šećerov, Bojana Lj., Ignjatović, Marija, Bilban, Martin, Anđus, Pavle R., El Refaei, Amal, Jung, Gangsoo, Li, Lin, Sase, Ajinkya, Chen, Weiqiang, Bačić, Goran, Lubec, Gert, "Erratum to: Radiation protection from whole-body gamma irradiation (6.7 Gy): behavioural effects and brain protein-level changes by an aminothiol compound GL2011 in the Wistar rat (vol 46, pg 1681, 2014)" in Amino Acids, 46, no. 10 (2014):2445-2445,
https://doi.org/10.1007/s00726-014-1791-2 . .

TY  - JOUR
AU  - Okić-Đorđević, Ivana
AU  - Trivanović, Drenka
AU  - Jovanović, Miloš
AU  - Ignjatović, Marija
AU  - Šećerov, Bojana Lj.
AU  - Mojovic, Milos
AU  - Bugarski, Diana
AU  - Bačić, Goran
AU  - Anđus, Pavle R.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5935
AB  - Aim To investigate the survival of laboratory rats after irradiation and to study the cellularity of their bone marrow and the multipotential mesenchymal stem cells (BM-MSCs) in groups treated with or without a new thiol-based radioprotector (GM2011) Methods Animals were irradiated by a Cobalt gamma source at 6.7 Gy. Treated animals were given i.p. GM2011 30 minutes before and 3 and 7 hours after irradiation. Controls consisted of sham irradiated animals without treatment and animals treated without irradiation. After 30 days post-irradiation, animals were sacrificed and bone marrow cells were prepared from isolated femurs. A colony forming unit-fibroblast (CFU-F) assay was performed to obtain the number of BM-MSCs. Results In the treated group, 87% of animals survived, compared to only 30% in the non-treated irradiated group. Irradiation induced significant changes in the bone marrow of the treated rats (total bone marrow cellularity was reduced by similar to 60% - from 63 to 28 cells x10(6)/femur and the frequency of the CFU-F per femur by similar to 70% - from 357 to 97), however GL2011 almost completely prevented the suppressive effect observed on day 30 post-irradiation (71 cells x 10(6)/femur and 230 CFU-F/femur). Conclusion Although the irradiation dosage was relatively high, GL2011 acted as a very effective new radioprotector. The recovery of the BN-MSCs and their counts support the effectiveness of the studied radioprotector.
T2  - Croatian Medical Journal
T1  - Increased survival after irradiation followed by regeneration of bone marrow stromal cells with a novel thiol-based radioprotector
VL  - 55
IS  - 1
SP  - 45
EP  - 49
DO  - 10.3325/cmj.2014.55.45
ER  - 

@article{
author = "Okić-Đorđević, Ivana and Trivanović, Drenka and Jovanović, Miloš and Ignjatović, Marija and Šećerov, Bojana Lj. and Mojovic, Milos and Bugarski, Diana and Bačić, Goran and Anđus, Pavle R.",
year = "2014",
abstract = "Aim To investigate the survival of laboratory rats after irradiation and to study the cellularity of their bone marrow and the multipotential mesenchymal stem cells (BM-MSCs) in groups treated with or without a new thiol-based radioprotector (GM2011) Methods Animals were irradiated by a Cobalt gamma source at 6.7 Gy. Treated animals were given i.p. GM2011 30 minutes before and 3 and 7 hours after irradiation. Controls consisted of sham irradiated animals without treatment and animals treated without irradiation. After 30 days post-irradiation, animals were sacrificed and bone marrow cells were prepared from isolated femurs. A colony forming unit-fibroblast (CFU-F) assay was performed to obtain the number of BM-MSCs. Results In the treated group, 87% of animals survived, compared to only 30% in the non-treated irradiated group. Irradiation induced significant changes in the bone marrow of the treated rats (total bone marrow cellularity was reduced by similar to 60% - from 63 to 28 cells x10(6)/femur and the frequency of the CFU-F per femur by similar to 70% - from 357 to 97), however GL2011 almost completely prevented the suppressive effect observed on day 30 post-irradiation (71 cells x 10(6)/femur and 230 CFU-F/femur). Conclusion Although the irradiation dosage was relatively high, GL2011 acted as a very effective new radioprotector. The recovery of the BN-MSCs and their counts support the effectiveness of the studied radioprotector.",
journal = "Croatian Medical Journal",
title = "Increased survival after irradiation followed by regeneration of bone marrow stromal cells with a novel thiol-based radioprotector",
volume = "55",
number = "1",
pages = "45-49",
doi = "10.3325/cmj.2014.55.45"
}

Okić-Đorđević, I., Trivanović, D., Jovanović, M., Ignjatović, M., Šećerov, B. Lj., Mojovic, M., Bugarski, D., Bačić, G.,& Anđus, P. R.. (2014). Increased survival after irradiation followed by regeneration of bone marrow stromal cells with a novel thiol-based radioprotector. in Croatian Medical Journal, 55(1), 45-49.
https://doi.org/10.3325/cmj.2014.55.45

Okić-Đorđević I, Trivanović D, Jovanović M, Ignjatović M, Šećerov BL, Mojovic M, Bugarski D, Bačić G, Anđus PR. Increased survival after irradiation followed by regeneration of bone marrow stromal cells with a novel thiol-based radioprotector. in Croatian Medical Journal. 2014;55(1):45-49.
doi:10.3325/cmj.2014.55.45 .

Okić-Đorđević, Ivana, Trivanović, Drenka, Jovanović, Miloš, Ignjatović, Marija, Šećerov, Bojana Lj., Mojovic, Milos, Bugarski, Diana, Bačić, Goran, Anđus, Pavle R., "Increased survival after irradiation followed by regeneration of bone marrow stromal cells with a novel thiol-based radioprotector" in Croatian Medical Journal, 55, no. 1 (2014):45-49,
https://doi.org/10.3325/cmj.2014.55.45 . .

TY  - JOUR
AU  - Ganesan, Minu Karthika
AU  - Jovanović, Miloš
AU  - Šećerov, Bojana Lj.
AU  - Ignjatović, Marija
AU  - Bilban, Martin
AU  - Anđus, Pavle R.
AU  - El Refaei, Amal
AU  - Jung, Gangsoo
AU  - Li, Lin
AU  - Sase, Ajinkya
AU  - Chen, Weiqiang
AU  - Bačić, Goran
AU  - Lubec, Gert
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/6052
AB  - GL2011 is a naturally occurring thiol compound and a series of thiol compounds have been proposed as radioprotectors. Radioprotective efficacy of a triple intraperitoneal dose of GL2011 of 100 mg/kg body weight of Wistar rats, 30 min prior to and 3 and 6 h following irradiation (6.7 Gy) was evaluated. Four groups of animals were used, vehicle-treated non-irradiated (VN), GL2011-treated and irradiated (GI), GL2011-treated and non-irradiated (GN) and vehicle-treated and irradiated (VI) (n = 30 per group). The radioprotective efficacy of GL2011 was determined by measuring 28-day survival and intestinal crypt cell survival. Neuroprotection in terms of behaviour was evaluated using the behavioural observational battery, open field test and elevated plus maze paradigm. An RNA microarray was carried out in order to show differences at the RNA level between VI and VN groups. Brain protein changes were identified using a gel-based proteomics method and major brain receptor complex levels were determined by blue-native gels followed by immunoblotting. 28-Day survival rate in VI was 30 %, in GI survival was 93 %, survival of VN and GN was 100 %. Jejunal crypt cell survival was significantly enhanced in GI. Protein-level changes of peroxiredoxin-5, Mn-superoxide dismutase 2, voltage-dependent anion-selective channel protein 1, septin 5 and dopamine D2 receptor complex levels were paralleling radiation damage and protection. Taken together, the findings demonstrate that GL2011 improves survival rates and jejunal crypt survival, provides partial neuroprotection at the behavioural level and modulates proteins known to be involved in protection against oxidative stress-mediated cell damage.
T2  - Amino Acids
T1  - Radiation protection from whole-body gamma irradiation (6.7 Gy): behavioural effects and brain protein-level changes by an aminothiol compound GL2011 in the Wistar rat
VL  - 46
IS  - 7
SP  - 1681
EP  - 1696
DO  - 10.1007/s00726-014-1728-9
ER  - 

@article{
author = "Ganesan, Minu Karthika and Jovanović, Miloš and Šećerov, Bojana Lj. and Ignjatović, Marija and Bilban, Martin and Anđus, Pavle R. and El Refaei, Amal and Jung, Gangsoo and Li, Lin and Sase, Ajinkya and Chen, Weiqiang and Bačić, Goran and Lubec, Gert",
year = "2014",
abstract = "GL2011 is a naturally occurring thiol compound and a series of thiol compounds have been proposed as radioprotectors. Radioprotective efficacy of a triple intraperitoneal dose of GL2011 of 100 mg/kg body weight of Wistar rats, 30 min prior to and 3 and 6 h following irradiation (6.7 Gy) was evaluated. Four groups of animals were used, vehicle-treated non-irradiated (VN), GL2011-treated and irradiated (GI), GL2011-treated and non-irradiated (GN) and vehicle-treated and irradiated (VI) (n = 30 per group). The radioprotective efficacy of GL2011 was determined by measuring 28-day survival and intestinal crypt cell survival. Neuroprotection in terms of behaviour was evaluated using the behavioural observational battery, open field test and elevated plus maze paradigm. An RNA microarray was carried out in order to show differences at the RNA level between VI and VN groups. Brain protein changes were identified using a gel-based proteomics method and major brain receptor complex levels were determined by blue-native gels followed by immunoblotting. 28-Day survival rate in VI was 30 %, in GI survival was 93 %, survival of VN and GN was 100 %. Jejunal crypt cell survival was significantly enhanced in GI. Protein-level changes of peroxiredoxin-5, Mn-superoxide dismutase 2, voltage-dependent anion-selective channel protein 1, septin 5 and dopamine D2 receptor complex levels were paralleling radiation damage and protection. Taken together, the findings demonstrate that GL2011 improves survival rates and jejunal crypt survival, provides partial neuroprotection at the behavioural level and modulates proteins known to be involved in protection against oxidative stress-mediated cell damage.",
journal = "Amino Acids",
title = "Radiation protection from whole-body gamma irradiation (6.7 Gy): behavioural effects and brain protein-level changes by an aminothiol compound GL2011 in the Wistar rat",
volume = "46",
number = "7",
pages = "1681-1696",
doi = "10.1007/s00726-014-1728-9"
}

Ganesan, M. K., Jovanović, M., Šećerov, B. Lj., Ignjatović, M., Bilban, M., Anđus, P. R., El Refaei, A., Jung, G., Li, L., Sase, A., Chen, W., Bačić, G.,& Lubec, G.. (2014). Radiation protection from whole-body gamma irradiation (6.7 Gy): behavioural effects and brain protein-level changes by an aminothiol compound GL2011 in the Wistar rat. in Amino Acids, 46(7), 1681-1696.
https://doi.org/10.1007/s00726-014-1728-9

Ganesan MK, Jovanović M, Šećerov BL, Ignjatović M, Bilban M, Anđus PR, El Refaei A, Jung G, Li L, Sase A, Chen W, Bačić G, Lubec G. Radiation protection from whole-body gamma irradiation (6.7 Gy): behavioural effects and brain protein-level changes by an aminothiol compound GL2011 in the Wistar rat. in Amino Acids. 2014;46(7):1681-1696.
doi:10.1007/s00726-014-1728-9 .

Ganesan, Minu Karthika, Jovanović, Miloš, Šećerov, Bojana Lj., Ignjatović, Marija, Bilban, Martin, Anđus, Pavle R., El Refaei, Amal, Jung, Gangsoo, Li, Lin, Sase, Ajinkya, Chen, Weiqiang, Bačić, Goran, Lubec, Gert, "Radiation protection from whole-body gamma irradiation (6.7 Gy): behavioural effects and brain protein-level changes by an aminothiol compound GL2011 in the Wistar rat" in Amino Acids, 46, no. 7 (2014):1681-1696,
https://doi.org/10.1007/s00726-014-1728-9 . .