Trimethyltin Increases Intracellular Ca2+ Via L-Type Voltage-Gated Calcium Channels and Promotes Inflammatory Phenotype in Rat Astrocytes In Vitro
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2021
Authors
Dragić, MiloradMilićević, Katarina
Adžić, Marija
Stevanović, Ivana
Ninković, Milica
Grković, Ivana
Anđus, Pavle
Nedeljković, Nadežda
Article (Published version)
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© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature
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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 o...n 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.
Keywords:
Astrocytes / Ca2+ dysregulation / L-type voltage-gated calcium channels / A1-like phenotype / TMT intoxicationSource:
Molecular Neurobiology, 2021, 58, 4, 1792-1805Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200178 (University of Belgrade, Faculty of Biology) (RS-MESTD-inst-2020-200178)
DOI: 10.1007/s12035-020-02273-x
ISSN: 0893-7648
PubMed: 33394334
WoS: 000604882300002
Scopus: 2-s2.0-85098992993
Institution/Community
VinčaTY - 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 . .