Iron uptake in quiescent and inflammation-activated astrocytes: A potentially neuroprotective control of iron burden

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1832

Article

Pelizzoni, Ilaria¹  Zacchetti, Daniele¹  Campanella, Alessandro¹  Grohovaz, Fabio^1,2  Codazzi, Franca¹ 

[1] Ist Sci San Raffaele, I-20132 Milan, Italy

[2] San Raffaele Univ, I-20132 Milan, Italy

关键词: Astrocytes;    Non-transferrin-bound iron uptake;    DMT1;    Activation process;    TRP channels;    Neuroinflammation;   

DOI  :  10.1016/j.bbadis.2013.04.007

来源: Elsevier

【 摘 要 】

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 I (DMTI) 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. (C) 2013 Elsevier B.V. All rights reserved.

【 授权许可】

Free