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Uptake of ferrous iron by cultured rat astrocytes
Author(s) -
Tulpule Ketki,
Robinson Stephen R.,
Bishop Glenda M.,
Dringen Ralf
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22217
Subject(s) - ferrous , ferric , dmt1 , chemistry , extracellular , biochemistry , astrocyte , transferrin , incubation , metabolism , ferric iron , ferritin , inorganic chemistry , biology , endocrinology , transporter , organic chemistry , gene , central nervous system
Astrocytes are considered to play an important role in iron homeostasis of the brain, yet the mechanisms involved in the uptake of iron into astrocytes remain elusive. To investigate the uptake of iron into astrocytes, we have applied ferric ammonium citrate (FAC) to rat astrocyte‐rich primary cultures. These cultures express the mRNAs of two membrane‐bound ferric reductases, Dcyt b and SDR2, and reduce extracellular ferric iron (100 μM) with a rate of 3.2 ± 0.4 nmol/(hr × mg). This reduction rate is substantially lower than the rate of cellular iron accumulation from 100 μM FAC [24.7 ± 8.9 nmol/(hr × mg)], which suggests that iron accumulation from FAC does at best partially depend on extracellular ferric reduction. Nonetheless, when the iron in FAC was almost completely reduced by an excess of exogenous ascorbate, astrocytes accumulated iron in a time‐ and concentration‐dependent manner with specific iron accumulation rates that increased linearly for concentrations of up to 100 μM ferrous iron. This accumulation was attenuated by lowering the incubation temperature, by the presence of ferrous iron chelators, or by lowering the pH from 7.4 to 6.8. These data indicate that, in addition to the DMT1‐mediated uptake of ferrous iron, astrocytes can accumulate ferric and ferrous iron by mechanisms that are independent of DMT1 or transferrin. © 2009 Wiley‐Liss, Inc.