Effects of Metformin on Spontaneous Ca2+ Signals in Cultured Microglia Cells under Normoxic and Hypoxic Conditions
| Autor: | Gytis Svirskis, Silvija Jankeviciute, Vilmante Borutaite, Natasa Svirskiene |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
microglia Phenformin Mitochondrial Membrane Transport Proteins chemistry.chemical_compound Cyclosporin a Biology (General) Spectroscopy chemistry.chemical_classification Neurons MPTP General Medicine Computer Science Applications Metformin Mitochondria Chemistry Cyclosporine Female medicine.symptom medicine.drug medicine.medical_specialty QH301-705.5 Ca2+ signals Primary Cell Culture Catalysis Article Inorganic Chemistry Internal medicine Caffeine Rotenone medicine Animals Calcium Signaling Physical and Theoretical Chemistry Chromans QD1-999 Molecular Biology phenformin Reactive oxygen species Electron Transport Complex I hypoxia Organic Chemistry mitochondrial permeability transition pore Hypoxia (medical) brain ischemia Rats Endocrinology chemistry Mitochondrial permeability transition pore Reactive Oxygen Species metformin |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 17 International Journal of Molecular Sciences, Vol 22, Iss 9493, p 9493 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22179493 |
| Popis: | Microglial functioning depends on Ca2+ signaling. By using Ca2+ sensitive fluorescence dye, we studied how inhibition of mitochondrial respiration changed spontaneous Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ homeostasis after mild hypoxia and could be important for reduction of ischemia-induced microglial activation. |
| Databáze: | OpenAIRE |
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