Iron induces two distinct Ca2+ signalling cascades in astrocytes
| Autor: | Alexei Verkhratsky, Manman Zhang, Baoman Li, Wenzheng Guan, Ming Ji, Shanshan Liang, Xinyu Li, Maosheng Xia, Beina Chen, Gehua Wen, Yuefei Zhou, Chengyi Dong, Dawei Guan, Dianjun Zhang, Shuai Li, Xiaoni Zhan, Binjie Chen, Wenliang Gong |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
QH301-705.5 Medicine (miscellaneous) Transferrin receptor General Biochemistry Genetics and Molecular Biology Ferrous 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Inositol Biology (General) chemistry.chemical_classification biology Phospholipase C Endoplasmic reticulum DMT1 030104 developmental biology chemistry Transferrin biology.protein Biophysics Ferric General Agricultural and Biological Sciences 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Communications Biology, Vol 4, Iss 1, Pp 1-13 (2021) |
| ISSN: | 2399-3642 |
| Popis: | Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe2+), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe3+). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca2+]i) in astrocytes. Administration of Fe2+ or Fe3+ in μM concentrations evoked [Ca2+]i in astrocytes in vitro and in vivo. Iron ions trigger increase in [Ca2+]i through two distinct molecular cascades. Uptake of Fe2+ by DMT1 inhibits astroglial Na+-K+-ATPase, which leads to elevation in cytoplasmic Na+ concentration, thus reversing Na+/Ca2+ exchanger and thereby generating Ca2+ influx. Uptake of Fe3+ by TF-TFR stimulates phospholipase C to produce inositol 1,4,5-trisphosphate (InsP3), thus triggering InsP3 receptor-mediated Ca2+ release from endoplasmic reticulum. In summary, these findings reveal the mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload. |
| Databáze: | OpenAIRE |
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