Iron induces two distinct Ca<sup>2+</sup> signalling cascades in astrocytes


  • Guan W.
  • Xia M.
  • Ji M.
  • Chen B.
  • Li S.
  • Zhang M.
  • Liang S.
  • Chen B.
  • Gong W.
  • Dong C.
  • Wen G.
  • Zhan X.
  • Zhang D.
  • Li X.
  • Zhou Y.
  • Guan D.
  • Verkhratsky A.
  • Li B.
Дата публикации:01.12.2021
Журнал: Communications Biology
БД: Scopus
Ссылка: Scopus

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


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