Аннтотация

Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe ), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe ). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca ] ) in astrocytes. Administration of Fe  or Fe  in μM concentrations evoked [Ca ]  in astrocytes in vitro and in vivo. Iron ions trigger increase in [Ca ]  through two distinct molecular cascades. Uptake of Fe  by DMT1 inhibits astroglial Na -K -ATPase, which leads to elevation in cytoplasmic Na  concentration, thus reversing Na /Ca  exchanger and thereby generating Ca  influx. Uptake of Fe  by TF-TFR stimulates phospholipase C to produce inositol 1,4,5-trisphosphate (InsP ), thus triggering InsP  receptor-mediated Ca  release from endoplasmic reticulum. In summary, these findings reveal the mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload. 2+ 3+ 2+ 2+ 3+ 2+ 2+ 2+ + + + + 2+ 2+ 3+ 2+ i i i 3 3