title: Uptake of ferrous iron by cultured rat astrocytes.
abstract: 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, Dcytb and SDR2, and reduce extracellular ferric iron (100 muM) with a rate of 3.2 +/- 0.4 nmol/(hr x mg). This reduction rate is substantially lower than the rate of cellular iron accumulation from 100 muM FAC [24.7 +/- 8.9 nmol/(hr x 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 muM 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.
authors.affiliation: Center for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany.
authors.forename: Ketki
authors.initials: K
authors.lastname: Tulpule
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Robinson
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Bishop
authors.forename: Ralf
authors.initials: R
authors.lastname: Dringen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D019343:Citric Acid / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005296:Ferrous Compounds / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D013997:Time Factors
chemical_list: D002614:Chelating Agents; D005296:Ferrous Compounds; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; D019343:Citric Acid; C481046:ammonium citrate; D007501:Iron; D010088:Oxidoreductases; C022690:succinic-dichloroindophenol reductase