Biomarkers in neurodegenerative and malignant processes

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Biomarkers in neurodegenerative and malignant processes (en)
Биомаркери у неуродегенеративним и малигним процесима (sr)
Biomarkeri u neurodegenerativnim i malignim procesima (sr_RS)
Authors

Publications

Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation Antioxidative System in BV-2 Microglial Cell Line

Milošević, Milena; Milićević, Katarina; Božić, Iva; Lavrnja, Irena; Stevanović, Ivana; Bijelić, Dunja; Dubaić, Marija; Živković, Irena; Stević, Zorica; Giniatullin, Rashid; Anđus, Pavle

(Frontiers Media Sa, Lausanne, 2017)

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  - Anđus, Pavle
PY  - 2017
UR  - http://intor.torlakinstitut.com/handle/123456789/482
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-alpha 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.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Immunology
T1  - Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation Antioxidative System in BV-2 Microglial Cell Line
VL  - 8
DO  - 10.3389/fimmu.2017.01619
UR  - conv_421
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 Anđus, 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-alpha 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.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Immunology",
title = "Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation Antioxidative System in BV-2 Microglial Cell Line",
volume = "8",
doi = "10.3389/fimmu.2017.01619",
url = "conv_421"
}
Milošević, M., Milićević, K., Božić, I., Lavrnja, I., Stevanović, I., Bijelić, D., Dubaić, M., Živković, I., Stević, Z., Giniatullin, R.,& Anđus, P.. (2017). Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation Antioxidative System in BV-2 Microglial Cell Line. in Frontiers in Immunology
Frontiers Media Sa, Lausanne., 8.
https://doi.org/10.3389/fimmu.2017.01619
conv_421
Milošević M, Milićević K, Božić I, Lavrnja I, Stevanović I, Bijelić D, Dubaić M, Živković I, Stević Z, Giniatullin R, Anđus P. Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation Antioxidative System in BV-2 Microglial Cell Line. in Frontiers in Immunology. 2017;8.
doi:10.3389/fimmu.2017.01619
conv_421 .
Milošević, Milena, Milićević, Katarina, Božić, Iva, Lavrnja, Irena, Stevanović, Ivana, Bijelić, Dunja, Dubaić, Marija, Živković, Irena, Stević, Zorica, Giniatullin, Rashid, Anđus, Pavle, "Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation Antioxidative System in BV-2 Microglial Cell Line" in Frontiers in Immunology, 8 (2017),
https://doi.org/10.3389/fimmu.2017.01619 .,
conv_421 .
1
15
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Immunoglobulins G from patients with sporadic amyotrophic lateral sclerosis affects cytosolic Ca2+ homeostasis in cultured rat astrocytes

Milošević, Milena; Stenovec, Matjaz; Kreft, Marko; Petrušić, Vladimir; Stević, Zorica; Trkov, Saša; Anđus, Pavle; Zorec, Robert

(Elsevier Sci Ltd, Oxford, 2013)

TY  - JOUR
AU  - Milošević, Milena
AU  - Stenovec, Matjaz
AU  - Kreft, Marko
AU  - Petrušić, Vladimir
AU  - Stević, Zorica
AU  - Trkov, Saša
AU  - Anđus, Pavle
AU  - Zorec, Robert
PY  - 2013
UR  - http://intor.torlakinstitut.com/handle/123456789/378
AB  - Astrocytes are considered essential in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). We have demonstrated previously that immunoglobulins G (IgG) isolated from patients with ALS enhance the mobility of acidic vesicles in cultured astrocytes in a Ca2+-dependent manner. Here we directly examined the impact of purified sporadic ALS IgG on cytosolic [Ca2+] ([Ca2+](i)) in astrocytes. Confocal time-lapse images were acquired and fluorescence of a non-ratiometric Ca2+ indicator was recorded before and after the application of IgG. ALS IgG (0.1 mg/ml) from 7 patients evoked transient increases in [Ca2+](i) in similar to 50% of tested astrocytes. The probability of observing a response was independent of extracellular Ca2+. The peak increase in [Ca2+](i) developed similar to 3 times faster and the time integral of evoked transients was similar to 2-fold larger; the peak amplitude itself was not affected by extracellular Ca2+. Application of pharmacological inhibitors revealed that activation of inositol-1,4,5-triphosphate receptors is necessary and sufficient to initiate transients in [Ca2+](i) the Ca2+ influx through store-operated calcium entry prolongs the transient increase in [Ca2+](i). Thus, ALS IgG acutely affect [Ca2+](i) by mobilizing both, intra- and extracellular Ca2+ into the cytosol of cultured astrocytes. (C) 2013 Elsevier Ltd. All rights reserved.
PB  - Elsevier Sci Ltd, Oxford
T2  - Cell Calcium
T1  - Immunoglobulins G from patients with sporadic amyotrophic lateral sclerosis affects cytosolic Ca2+ homeostasis in cultured rat astrocytes
EP  - 25
IS  - 1
SP  - 17
VL  - 54
DO  - 10.1016/j.ceca.2013.03.005
UR  - conv_309
ER  - 
@article{
author = "Milošević, Milena and Stenovec, Matjaz and Kreft, Marko and Petrušić, Vladimir and Stević, Zorica and Trkov, Saša and Anđus, Pavle and Zorec, Robert",
year = "2013",
abstract = "Astrocytes are considered essential in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). We have demonstrated previously that immunoglobulins G (IgG) isolated from patients with ALS enhance the mobility of acidic vesicles in cultured astrocytes in a Ca2+-dependent manner. Here we directly examined the impact of purified sporadic ALS IgG on cytosolic [Ca2+] ([Ca2+](i)) in astrocytes. Confocal time-lapse images were acquired and fluorescence of a non-ratiometric Ca2+ indicator was recorded before and after the application of IgG. ALS IgG (0.1 mg/ml) from 7 patients evoked transient increases in [Ca2+](i) in similar to 50% of tested astrocytes. The probability of observing a response was independent of extracellular Ca2+. The peak increase in [Ca2+](i) developed similar to 3 times faster and the time integral of evoked transients was similar to 2-fold larger; the peak amplitude itself was not affected by extracellular Ca2+. Application of pharmacological inhibitors revealed that activation of inositol-1,4,5-triphosphate receptors is necessary and sufficient to initiate transients in [Ca2+](i) the Ca2+ influx through store-operated calcium entry prolongs the transient increase in [Ca2+](i). Thus, ALS IgG acutely affect [Ca2+](i) by mobilizing both, intra- and extracellular Ca2+ into the cytosol of cultured astrocytes. (C) 2013 Elsevier Ltd. All rights reserved.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Cell Calcium",
title = "Immunoglobulins G from patients with sporadic amyotrophic lateral sclerosis affects cytosolic Ca2+ homeostasis in cultured rat astrocytes",
pages = "25-17",
number = "1",
volume = "54",
doi = "10.1016/j.ceca.2013.03.005",
url = "conv_309"
}
Milošević, M., Stenovec, M., Kreft, M., Petrušić, V., Stević, Z., Trkov, S., Anđus, P.,& Zorec, R.. (2013). Immunoglobulins G from patients with sporadic amyotrophic lateral sclerosis affects cytosolic Ca2+ homeostasis in cultured rat astrocytes. in Cell Calcium
Elsevier Sci Ltd, Oxford., 54(1), 17-25.
https://doi.org/10.1016/j.ceca.2013.03.005
conv_309
Milošević M, Stenovec M, Kreft M, Petrušić V, Stević Z, Trkov S, Anđus P, Zorec R. Immunoglobulins G from patients with sporadic amyotrophic lateral sclerosis affects cytosolic Ca2+ homeostasis in cultured rat astrocytes. in Cell Calcium. 2013;54(1):17-25.
doi:10.1016/j.ceca.2013.03.005
conv_309 .
Milošević, Milena, Stenovec, Matjaz, Kreft, Marko, Petrušić, Vladimir, Stević, Zorica, Trkov, Saša, Anđus, Pavle, Zorec, Robert, "Immunoglobulins G from patients with sporadic amyotrophic lateral sclerosis affects cytosolic Ca2+ homeostasis in cultured rat astrocytes" in Cell Calcium, 54, no. 1 (2013):17-25,
https://doi.org/10.1016/j.ceca.2013.03.005 .,
conv_309 .
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