Dataset Information

Iron induces two distinct Ca²⁺ signalling cascades in astrocytes.

ABSTRACT: Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe²⁺), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe³⁺). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca²⁺]_i) in astrocytes. Administration of Fe²⁺ or Fe³⁺ in μM concentrations evoked [Ca²⁺]_i in astrocytes in vitro and in vivo. Iron ions trigger increase in [Ca²⁺]_i through two distinct molecular cascades. Uptake of Fe²⁺ by DMT1 inhibits astroglial Na⁺-K⁺-ATPase, which leads to elevation in cytoplasmic Na⁺ concentration, thus reversing Na⁺/Ca²⁺ exchanger and thereby generating Ca²⁺ influx. Uptake of Fe³⁺ by TF-TFR stimulates phospholipase C to produce inositol 1,4,5-trisphosphate (InsP₃), thus triggering InsP₃ receptor-mediated Ca²⁺ release from endoplasmic reticulum. In summary, these findings reveal the mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload.

SUBMITTER: Guan W

PROVIDER: S-EPMC8100120 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Introduction: Safranal, which endows saffron its unique aroma, causes vasodilatation and has a hypotensive effect in animal studies, but the mechanisms of these effects are unknown. In this study, we investigated the mechanisms of safranal vasodilation. Methods: Isolated rat endothelium-intact or -denuded aortic rings were precontracted with phenylephrine and then relaxed with safranal. To further assess the involvement of nitric oxide, prostaglandins, guanylate cyclase, and phospholipase A2 in safranal-induced vasodilation, aortic rings were preincubated with L-NAME, indomethacin, methylene blue, or quinacrine, respectively, then precontracted with phenylephrine, and safranal concentration-response curves were established. To explore the effects of safranal on Ca2+ influx, phenylephrine and CaCl2 concentration-response curves were established in the presence of safranal. Furthermore, the effect of safranal on aortic rings in the presence of ouabain, a Na+-K+ ATPase inhibitor, was studied to explore the contribution of Na+/Ca2+ exchanger to this vasodilation. Results: Safranal caused vasodilation in endothelium-intact and endothelium-denuded aortic rings. The vasodilation was not eliminated by pretreatment with L-NAME, indomethacin, methylene blue, or quinacrine, indicating the lack of a role for NO/cGMP. Safranal significantly inhibited the maximum contractions induced by phenylephrine, or by CaCl2 in Ca2+-free depolarizing buffer. Safranal also relaxed contractions induced by ouabain, but pretreatment with safranal totally abolished the development of ouabain contractions. Discussion/Conclusion: Inhibition of Na+-K+ ATPase by ouabain leads to the accumulation of Na+ intracellularly, forcing the Na+/Ca2+ exchanger to work in reverse mode, thus causing a contraction. Inhibition of the development of this contraction by preincubation with safranal indicates that safranal inhibited the Na+/Ca2+ exchanger. We conclude that safranal vasodilation is mediated by the inhibition of calcium influx from extracellular space through L-type Ca2+ channels and by the inhibition of the Na+/Ca2+ exchanger.

Dataset Information

Iron induces two distinct Ca²⁺ signalling cascades in astrocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Iron induces two distinct Ca2+ signalling cascades in astrocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Iron induces two distinct Ca²⁺ signalling cascades in astrocytes.