• Iron induces two distinct Ca

      Guan, Wenzheng; Xia, Maosheng; Ji, Ming; Chen, Beina; Li, Shuai; Zhang, Manman; Liang, Shanshan; Chen, Binjie; Gong, Wenliang; Dong, Chengyi; et al. (2021-05-05)
      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.
    • Iron induces two distinct Ca<sup>2+</sup> signalling cascades in astrocytes.

      Guan, Wenzheng; Xia, Maosheng; Ji, Ming; Chen, Beina; Li, Shuai; Zhang, Manman; Liang, Shanshan; Chen, Binjie; Gong, Wenliang; Dong, Chengyi; et al. (2021-05-05)
      Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe<sup>2+</sup>), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe<sup>3+</sup>). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca<sup>2+</sup>]<sub>i</sub>) in astrocytes. Administration of Fe<sup>2+</sup> or Fe<sup>3+</sup> in μM concentrations evoked [Ca<sup>2+</sup>]<sub>i</sub> in astrocytes in vitro and in vivo. Iron ions trigger increase in [Ca<sup>2+</sup>]<sub>i</sub> through two distinct molecular cascades. Uptake of Fe<sup>2+</sup> by DMT1 inhibits astroglial Na<sup>+</sup>-K<sup>+</sup>-ATPase, which leads to elevation in cytoplasmic Na<sup>+</sup> concentration, thus reversing Na<sup>+</sup>/Ca<sup>2+</sup> exchanger and thereby generating Ca<sup>2+</sup> influx. Uptake of Fe<sup>3+</sup> by TF-TFR stimulates phospholipase C to produce inositol 1,4,5-trisphosphate (InsP<sub>3</sub>), thus triggering InsP<sub>3</sub> receptor-mediated Ca<sup>2+</sup> release from endoplasmic reticulum. In summary, these findings reveal the mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload.