Iron uptake in quiescent and inflammation-activated astrocytes: A potentially neuroprotective control of iron burden
| Autor: | Fabio Grohovaz, Ilaria Pelizzoni, Daniele Zacchetti, Franca Codazzi, Alessandro Campanella |
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| Přispěvatelé: | Pelizzoni, I, Zacchetti, D, Campanella, A, Grohovaz, Fabio, Codazzi, Franca |
| Jazyk: | angličtina |
| Předmět: |
FAC
ferric ammonium citrate NMDA N-Methyl-d-aspartate medicine.disease_cause Ferric Compounds Hippocampus Rats Sprague-Dawley Transient receptor potential channel Transient Receptor Potential Channels TfR1 transferrin receptor 1 Neuroinflammation BBB blood–brain barrier Cation Transport Proteins DMT1 Cells Cultured chemistry.chemical_classification Neurons TNF tumor necrosis factor biology EYFP enhanced yellow fluorescent protein TIRF microscopy total internal reflection fluorescence microscopy Transferrin Long-term potentiation Cell biology DHPG dihydroxyphenylglycine Biochemistry NTBI non-transferrin-bound-iron Molecular Medicine TRP transient receptor potential TBI Tf-bound iron LIP labile iron pool Iron TRPV1 Neuroprotection Article DMT1 divalent metal transporter 1 PLC phospholipase C Tf transferrin medicine TRPV1 transient receptor potential vanilloid 1 Non-transferrin-bound iron uptake Animals IFN interferon Ferrous Compounds Molecular Biology Inflammation Activation process TRP channels FAS ferrous ammonium sulfate VOCCs voltage-operated calcium channels Rats IL interleukin Oxidative Stress chemistry Astrocytes biology.protein Oxidative stress |
| Zdroj: | Biochimica et Biophysica Acta |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2013.04.007 |
| Popis: | Astrocytes play a crucial role in proper iron handling within the central nervous system. This competence can be fundamental, particularly during neuroinflammation, and neurodegenerative processes, where an increase in iron content can favor oxidative stress, thereby worsening disease progression. Under these pathological conditions, astrocytes undergo a process of activation that confers them either a beneficial or a detrimental role on neuronal survival. Our work investigates the mechanisms of iron entry in cultures of quiescent and activated hippocampal astrocytes. Our data confirm that the main source of iron is the non-transferrin-bound iron (NTBI) and show the involvement of two different routes for its entry: the resident transient receptor potential (TRP) channels in quiescent astrocytes and the de novo expressed divalent metal transporter 1 (DMT1) in activated astrocytes, which accounts for a potentiation of iron entry. Overall, our data suggest that at rest, but even more after activation, astrocytes have the potential to buffer the excess of iron, thereby protecting neurons from iron overload. These findings further extend our understanding of the protective role of astrocytes under the conditions of iron-mediated oxidative stress observed in several neurodegenerative conditions. Highlights • Non-transferrin-bound iron (NTBI) is the main source of iron for astrocytes. • TRPC channels represent an entry pathway for Fe2 + in resting astrocytes. • Activation process increases the competence of astrocytes to uptake iron. • DMT1 expression accounts for potentiation of iron ingress in activated astrocytes. |
| Databáze: | OpenAIRE |
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