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Effects of Metformin on Spontaneous Ca(2+) Signals in Cultured Microglia Cells under Normoxic and Hypoxic Conditions

Microglial functioning depends on Ca(2+) signaling. By using Ca(2+) sensitive fluorescence dye, we studied how inhibition of mitochondrial respiration changed spontaneous Ca(2+) signals in soma of microglial cells from 5–7-day-old rats grown under normoxic and mild-hypoxic conditions. In microglia u...

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Autores principales: Jankeviciute, Silvija, Svirskiene, Natasa, Svirskis, Gytis, Borutaite, Vilmante
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430509/
https://www.ncbi.nlm.nih.gov/pubmed/34502402
http://dx.doi.org/10.3390/ijms22179493
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author Jankeviciute, Silvija
Svirskiene, Natasa
Svirskis, Gytis
Borutaite, Vilmante
author_facet Jankeviciute, Silvija
Svirskiene, Natasa
Svirskis, Gytis
Borutaite, Vilmante
author_sort Jankeviciute, Silvija
collection PubMed
description Microglial functioning depends on Ca(2+) signaling. By using Ca(2+) sensitive fluorescence dye, we studied how inhibition of mitochondrial respiration changed spontaneous Ca(2+) signals in soma of microglial cells from 5–7-day-old rats grown under normoxic and mild-hypoxic conditions. In microglia under normoxic conditions, metformin or rotenone elevated the rate and the amplitude of Ca(2+) signals 10–15 min after drug application. Addition of cyclosporin A, a blocker of mitochondrial permeability transition pore (mPTP), antioxidant trolox, or inositol 1,4,5-trisphosphate receptor (IP3R) blocker caffeine in the presence of rotenone reduced the elevated rate and the amplitude of the signals implying sensitivity to reactive oxygen species (ROS), and involvement of mitochondrial mPTP together with IP3R. Microglial cells exposed to mild hypoxic conditions for 24 h showed elevated rate and increased amplitude of Ca(2+) signals. Application of metformin or rotenone but not phenformin before mild hypoxia reduced this elevated rate. Thus, metformin and rotenone had the opposing fast action in normoxia after 10–15 min and the slow action during 24 h mild-hypoxia implying activation of different signaling pathways. The slow action of metformin through inhibition of complex I could stabilize Ca(2+) homeostasis after mild hypoxia and could be important for reduction of ischemia-induced microglial activation.
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spelling pubmed-84305092021-09-11 Effects of Metformin on Spontaneous Ca(2+) Signals in Cultured Microglia Cells under Normoxic and Hypoxic Conditions Jankeviciute, Silvija Svirskiene, Natasa Svirskis, Gytis Borutaite, Vilmante Int J Mol Sci Article Microglial functioning depends on Ca(2+) signaling. By using Ca(2+) sensitive fluorescence dye, we studied how inhibition of mitochondrial respiration changed spontaneous Ca(2+) signals in soma of microglial cells from 5–7-day-old rats grown under normoxic and mild-hypoxic conditions. In microglia under normoxic conditions, metformin or rotenone elevated the rate and the amplitude of Ca(2+) signals 10–15 min after drug application. Addition of cyclosporin A, a blocker of mitochondrial permeability transition pore (mPTP), antioxidant trolox, or inositol 1,4,5-trisphosphate receptor (IP3R) blocker caffeine in the presence of rotenone reduced the elevated rate and the amplitude of the signals implying sensitivity to reactive oxygen species (ROS), and involvement of mitochondrial mPTP together with IP3R. Microglial cells exposed to mild hypoxic conditions for 24 h showed elevated rate and increased amplitude of Ca(2+) signals. Application of metformin or rotenone but not phenformin before mild hypoxia reduced this elevated rate. Thus, metformin and rotenone had the opposing fast action in normoxia after 10–15 min and the slow action during 24 h mild-hypoxia implying activation of different signaling pathways. The slow action of metformin through inhibition of complex I could stabilize Ca(2+) homeostasis after mild hypoxia and could be important for reduction of ischemia-induced microglial activation. MDPI 2021-08-31 /pmc/articles/PMC8430509/ /pubmed/34502402 http://dx.doi.org/10.3390/ijms22179493 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jankeviciute, Silvija
Svirskiene, Natasa
Svirskis, Gytis
Borutaite, Vilmante
Effects of Metformin on Spontaneous Ca(2+) Signals in Cultured Microglia Cells under Normoxic and Hypoxic Conditions
title Effects of Metformin on Spontaneous Ca(2+) Signals in Cultured Microglia Cells under Normoxic and Hypoxic Conditions
title_full Effects of Metformin on Spontaneous Ca(2+) Signals in Cultured Microglia Cells under Normoxic and Hypoxic Conditions
title_fullStr Effects of Metformin on Spontaneous Ca(2+) Signals in Cultured Microglia Cells under Normoxic and Hypoxic Conditions
title_full_unstemmed Effects of Metformin on Spontaneous Ca(2+) Signals in Cultured Microglia Cells under Normoxic and Hypoxic Conditions
title_short Effects of Metformin on Spontaneous Ca(2+) Signals in Cultured Microglia Cells under Normoxic and Hypoxic Conditions
title_sort effects of metformin on spontaneous ca(2+) signals in cultured microglia cells under normoxic and hypoxic conditions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430509/
https://www.ncbi.nlm.nih.gov/pubmed/34502402
http://dx.doi.org/10.3390/ijms22179493
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