Immunoglobulins G from patients with sporadic amyotrophic lateral sclerosis affects cytosolic Ca2+ homeostasis in cultured rat astrocytes
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2013
Authors
Milošević, MilenaStenovec, Matjaz
Kreft, Marko
Petrušić, Vladimir
Stević, Zorica
Trkov, Saša
Anđus, Pavle
Zorec, Robert
Article (Published version)
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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 tha...t 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.
Keywords:
Amyotrophic lateral sclerosis / Astrocytes / IgG / Calcium homeostasis / IP3 receptorsSource:
Cell Calcium, 2013, 54, 1, 17-25Publisher:
- Elsevier Sci Ltd, Oxford
Funding / projects:
- Slovenian Research Agency (ARRS)Slovenian Research Agency - Slovenia [P3 310 0381]
- EduGlia ESR grant
- Biomarkers in neurodegenerative and malignant processes (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41005)
DOI: 10.1016/j.ceca.2013.03.005
ISSN: 0143-4160
PubMed: 23623373
WoS: 000320681000002
Scopus: 2-s2.0-84878218847
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TorlakTY - 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 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" }
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
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 .
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 . .