TY  - CONF
AU  - Milićević, Katarina
AU  - Milošević, Milena
AU  - Božić, Iva
AU  - Lavrnja, Irena
AU  - Stevanović, Ivana
AU  - Bijelić, Dunja D.
AU  - Živković, Irena
AU  - Stević, Zorica
AU  - Anđus, Pavle R.
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5990
AB  - Introduction. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects motor neurons. Having in mind well documented facts that on one hand, ALS brain is under oxidative stress, and on the other that non-cell autonomous mechanisms involving glial cells contribute to the disease progression, we wanted to examine the effect of humoral factors immunoglobulins G from ALS patients (ALS IgG) on oxidative stress and antioxidative system of BV-2 microglial cell line. Methods. BV-2 cells were treated with ALS and control IgG (0.1 mg/ml). TNF-α release, oxidative stress markers and antioxidative enzymes activities were determined using biochemical assays (24 h treatment), while gene expression was determined using RT-qPCR (4 h treatment). ROS, cytosolic peroxide and pH alteration were evaluated with carboxy-H2DCFDA, HyPer and SypHer, respectively. Results. All tested ALS IgG (compared with control IgG) induced oxidative stress (rise in NO and lipid peroxidation), release of TNF-α and higher antioxidative defense (elevation of Mn- and Cu,Zn-superoxide dismutase, catalase, glutathione reductase with a decrease of glutathione peroxidase and glutathione). IgG from 4/11 ALS patients induced slow exponential rise of HyPer intensity and lower increase of SypHer intensity. None of the control IgG induced changes with neither of the indicators. Acute ROS generation was detected in 1/3 of ALS samples with carboxy-H2DCFDA. Conclusion. Our study demonstrates the potential role of inflammatory humoral factors, ALS IgGs, as triggers (via ROS generation) of the activation in microglia, known to occur in later stages of the disease.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia
T1  - Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line
SP  - 72
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5990
ER  - 

@conference{
author = "Milićević, Katarina and Milošević, Milena and Božić, Iva and Lavrnja, Irena and Stevanović, Ivana and Bijelić, Dunja D. and Živković, Irena and Stević, Zorica and Anđus, Pavle R.",
year = "2017",
abstract = "Introduction. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects motor neurons. Having in mind well documented facts that on one hand, ALS brain is under oxidative stress, and on the other that non-cell autonomous mechanisms involving glial cells contribute to the disease progression, we wanted to examine the effect of humoral factors immunoglobulins G from ALS patients (ALS IgG) on oxidative stress and antioxidative system of BV-2 microglial cell line. Methods. BV-2 cells were treated with ALS and control IgG (0.1 mg/ml). TNF-α release, oxidative stress markers and antioxidative enzymes activities were determined using biochemical assays (24 h treatment), while gene expression was determined using RT-qPCR (4 h treatment). ROS, cytosolic peroxide and pH alteration were evaluated with carboxy-H2DCFDA, HyPer and SypHer, respectively. Results. All tested ALS IgG (compared with control IgG) induced oxidative stress (rise in NO and lipid peroxidation), release of TNF-α and higher antioxidative defense (elevation of Mn- and Cu,Zn-superoxide dismutase, catalase, glutathione reductase with a decrease of glutathione peroxidase and glutathione). IgG from 4/11 ALS patients induced slow exponential rise of HyPer intensity and lower increase of SypHer intensity. None of the control IgG induced changes with neither of the indicators. Acute ROS generation was detected in 1/3 of ALS samples with carboxy-H2DCFDA. Conclusion. Our study demonstrates the potential role of inflammatory humoral factors, ALS IgGs, as triggers (via ROS generation) of the activation in microglia, known to occur in later stages of the disease.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia",
title = "Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line",
pages = "72",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5990"
}

Milićević, K., Milošević, M., Božić, I., Lavrnja, I., Stevanović, I., Bijelić, D. D., Živković, I., Stević, Z.,& Anđus, P. R.. (2017). Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line. in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 72.
https://hdl.handle.net/21.15107/rcub_ibiss_5990

Milićević K, Milošević M, Božić I, Lavrnja I, Stevanović I, Bijelić DD, Živković I, Stević Z, Anđus PR. Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line. in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia. 2017;:72.
https://hdl.handle.net/21.15107/rcub_ibiss_5990 .

Milićević, Katarina, Milošević, Milena, Božić, Iva, Lavrnja, Irena, Stevanović, Ivana, Bijelić, Dunja D., Živković, Irena, Stević, Zorica, Anđus, Pavle R., "Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line" in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia (2017):72,
https://hdl.handle.net/21.15107/rcub_ibiss_5990 .

TY  - JOUR
AU  - Milošević, Milena
AU  - Milićević, Katarina
AU  - Božić, Iva
AU  - Lavrnja, Irena
AU  - Stevanović, Ivana
AU  - Bijelić, Dunja
AU  - Dubaić, Marija
AU  - Živković, Irena
AU  - Stević, Zorica
AU  - Giniatullin, Rashid
AU  - Andjus, Pavle
PY  - 2017
UR  - http://journal.frontiersin.org/article/10.3389/fimmu.2017.01619/full
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2928
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a very fast progression, no diagnostic tool for the presymptomatic phase, and still no effective treatment of the disease. Although ALS affects motor neurons, the overall pathophysiological condition points out to the non-cell autonomous mechanisms, where astrocytes and microglia play crucial roles in the disease progression. We have already shown that IgG from sera of ALS patients (ALS IgG) induce calcium transients and an increase in the mobility of acidic vesicles in cultured rat astrocytes. Having in mind the role of microglia in neurodegeneration, and a well-documented fact that oxidative stress is one of the many components contributing to the disease, we decided to examine the effect of ALS IgG on activation, oxidative stress and antioxidative system of BV-2 microglia, and to evaluate their acute effect on cytosolic peroxide, pH, and on reactive oxygen species (ROS) generation. All tested ALS IgGs (compared to control IgG) induced oxidative stress (rise in nitric oxide and the index of lipid peroxidation) followed by release of TNF-α and higher antioxidative defense (elevation of Mn- and CuZn-superoxide dismutase, catalase, and glutathione reductase with a decrease of glutathione peroxidase and glutathione) after 24 h treatment. Both ALS IgG and control IgG showed same localization on the membrane of BV-2 cells following 24 h treatment. Cytosolic peroxide and pH alteration were evaluated with fluorescent probes HyPer and SypHer, respectively, having in mind that HyPer also reacts to pH changes. Out of 11 tested IgGs from ALS patients, 4 induced slow exponential rise of HyPer signal, with maximal normalized fluorescence in the range 0.2–0.5, also inducing similar increase of SypHer intensity, but of a lower amplitude. None of the control IgGs induced changes with neither of the indicators. Acute ROS generation was detected in one out of three tested ALS samples with carboxy-H2DCFDA. The observed phenomena demonstrate the potential role of inflammatory humoral factors, IgGs, as potential triggers of the activation in microglia, known to occur in later stages of ALS. Therefore, revealing the ALS IgG signaling cascade in microglial cells could offer a valuable molecular biomarker and/or a potential therapeutic target.
T2  - Frontiers in Immunology
T1  - Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line
IS  - NOV
VL  - 8
DO  - 10.3389/fimmu.2017.01619
SP  - 1619
ER  - 

@article{
author = "Milošević, Milena and Milićević, Katarina and Božić, Iva and Lavrnja, Irena and Stevanović, Ivana and Bijelić, Dunja and Dubaić, Marija and Živković, Irena and Stević, Zorica and Giniatullin, Rashid and Andjus, Pavle",
year = "2017",
abstract = "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a very fast progression, no diagnostic tool for the presymptomatic phase, and still no effective treatment of the disease. Although ALS affects motor neurons, the overall pathophysiological condition points out to the non-cell autonomous mechanisms, where astrocytes and microglia play crucial roles in the disease progression. We have already shown that IgG from sera of ALS patients (ALS IgG) induce calcium transients and an increase in the mobility of acidic vesicles in cultured rat astrocytes. Having in mind the role of microglia in neurodegeneration, and a well-documented fact that oxidative stress is one of the many components contributing to the disease, we decided to examine the effect of ALS IgG on activation, oxidative stress and antioxidative system of BV-2 microglia, and to evaluate their acute effect on cytosolic peroxide, pH, and on reactive oxygen species (ROS) generation. All tested ALS IgGs (compared to control IgG) induced oxidative stress (rise in nitric oxide and the index of lipid peroxidation) followed by release of TNF-α and higher antioxidative defense (elevation of Mn- and CuZn-superoxide dismutase, catalase, and glutathione reductase with a decrease of glutathione peroxidase and glutathione) after 24 h treatment. Both ALS IgG and control IgG showed same localization on the membrane of BV-2 cells following 24 h treatment. Cytosolic peroxide and pH alteration were evaluated with fluorescent probes HyPer and SypHer, respectively, having in mind that HyPer also reacts to pH changes. Out of 11 tested IgGs from ALS patients, 4 induced slow exponential rise of HyPer signal, with maximal normalized fluorescence in the range 0.2–0.5, also inducing similar increase of SypHer intensity, but of a lower amplitude. None of the control IgGs induced changes with neither of the indicators. Acute ROS generation was detected in one out of three tested ALS samples with carboxy-H2DCFDA. The observed phenomena demonstrate the potential role of inflammatory humoral factors, IgGs, as potential triggers of the activation in microglia, known to occur in later stages of ALS. Therefore, revealing the ALS IgG signaling cascade in microglial cells could offer a valuable molecular biomarker and/or a potential therapeutic target.",
journal = "Frontiers in Immunology",
title = "Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line",
number = "NOV",
volume = "8",
doi = "10.3389/fimmu.2017.01619",
pages = "1619"
}

Milošević, M., Milićević, K., Božić, I., Lavrnja, I., Stevanović, I., Bijelić, D., Dubaić, M., Živković, I., Stević, Z., Giniatullin, R.,& Andjus, P.. (2017). Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line. in Frontiers in Immunology, 8(NOV), 1619.
https://doi.org/10.3389/fimmu.2017.01619

Milošević M, Milićević K, Božić I, Lavrnja I, Stevanović I, Bijelić D, Dubaić M, Živković I, Stević Z, Giniatullin R, Andjus P. Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line. in Frontiers in Immunology. 2017;8(NOV):1619.
doi:10.3389/fimmu.2017.01619 .

Milošević, Milena, Milićević, Katarina, Božić, Iva, Lavrnja, Irena, Stevanović, Ivana, Bijelić, Dunja, Dubaić, Marija, Živković, Irena, Stević, Zorica, Giniatullin, Rashid, Andjus, Pavle, "Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line" in Frontiers in Immunology, 8, no. NOV (2017):1619,
https://doi.org/10.3389/fimmu.2017.01619 . .