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铁在星形胶质细胞中诱导两种不同的钙信号级联反应。

Iron induces two distinct Ca signalling cascades in astrocytes.

机构信息

Practical Teaching Centre, School of Forensic Medicine, China Medical University, Shenyang, PR China.

The First Department of Reproduction, Shengjing Hospital, China Medical University, Shenyang, China.

出版信息

Commun Biol. 2021 May 5;4(1):525. doi: 10.1038/s42003-021-02060-x.

DOI:10.1038/s42003-021-02060-x
PMID:33953326
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8100120/
Abstract

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.

摘要

铁是许多生理功能的基本元素。质膜二价金属离子转运蛋白 1（DMT1）负责细胞内亚铁（Fe）的摄取，而转铁蛋白受体（TFR）则携带转铁蛋白（TF）结合的三价铁（Fe）。在这项研究中，我们对 Fe 离子在星形胶质细胞细胞质游离钙离子浓度（[Ca]）中的作用进行了详细分析。Fe 或 Fe 在 μM 浓度下的给药在体外和体内均会引发星形胶质细胞的 [Ca]增加。铁离子通过两个不同的分子级联触发 [Ca]的增加。DMT1 摄取 Fe 会抑制星形胶质细胞的 Na-K-ATP 酶，从而导致细胞质 Na 浓度升高，从而逆转 Na/Ca 交换体，从而产生 Ca 内流。TF-TFR 摄取的 Fe 会刺激磷脂酶 C 产生肌醇 1,4,5-三磷酸（InsP），从而触发内质网中 InsP 受体介导的 Ca 释放。总之，这些发现揭示了铁过载条件下铁诱导星形胶质细胞信号转导的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/e2fbbbaf3aa8/42003_2021_2060_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/f7a2f306e988/42003_2021_2060_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/27e746814b90/42003_2021_2060_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/3aa7803b2be7/42003_2021_2060_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/24e7335f7fa0/42003_2021_2060_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/eac825bff057/42003_2021_2060_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/d68f7ff10620/42003_2021_2060_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/e2fbbbaf3aa8/42003_2021_2060_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/f7a2f306e988/42003_2021_2060_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/27e746814b90/42003_2021_2060_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/3aa7803b2be7/42003_2021_2060_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/24e7335f7fa0/42003_2021_2060_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/eac825bff057/42003_2021_2060_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/d68f7ff10620/42003_2021_2060_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/8100120/e2fbbbaf3aa8/42003_2021_2060_Fig7_HTML.jpg

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