Article ; Online: Hypoxia induces an increase in intracellular magnesium via transient receptor potential melastatin 7 (TRPM7) channels in rat hippocampal neurons in vitro.
The Journal of biological chemistry
2011 Volume 286, Issue 23, Page(s) 20194–20207
Abstract: ... transported via a TRPM7 channel into the intracellular space of rat hippocampal neurons after 1 h of oxygen ... These results suggest that anoxia induced the increase of [Mg(2+)](i) via TRPM7 channels in rat hippocampal ... with shRNA in hippocampal neurons, it was found that not only was the increase of [Mg(2+)](i) induced by OGD ...
| Abstract | TRPM7, a divalent cation channel, plays an important role in neurons damaged from cerebral ischemia due to permitting intracellular calcium overload. This study aimed to explore whether magnesium was transported via a TRPM7 channel into the intracellular space of rat hippocampal neurons after 1 h of oxygen-glucose deprivation (OGD) and acute chemical ischemia (CI) by using methods of the Mg(2+) fluorescent probe Mag-Fura-2 to detect intracellular magnesium concentration ([Mg(2+)](i)) and flame atomic absorption spectrometry to measure extracellular magnesium concentration ([Mg(2+)](o)). The results showed that the neuronal [Mg(2+)](i) was 1.51-fold higher after 1 h of OGD at a basal level, and the increase of neuronal [Mg(2+)](i) reached a peak after 1 h of OGD and was kept for 60 min with re-oxygenation. Meanwhile, the [Mg(2+)](o) decreased after 1 h of OGD and recovered to the pre-ischemic level within 15 min after re-oxygenation. In the case of CI, the [Mg(2+)](i) peak immediately appeared in hippocampal neurons. This increase of [Mg(2+)](i) declined by removing extracellular magnesium in OGD or CI. Furthermore, by using Gd(3+) or 2-aminoethoxydiphenyl borate to inhibit TRPM7 channels, the [Mg(2+)](i) increase, which was induced by OGD or CI, was attenuated without altering the basal level of [Mg(2+)](i). By silencing TRPM7 with shRNA in hippocampal neurons, it was found that not only was the increase of [Mg(2+)](i) induced by OGD or CI but also the basal levels of [Mg(2+)](i) were attenuated. In contrast, overexpression of TRPM7 in HEK293 cells exaggerated both the basal levels and increased [Mg(2+)](i) after 1 h of OGD/CI. These results suggest that anoxia induced the increase of [Mg(2+)](i) via TRPM7 channels in rat hippocampal neurons. |
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| MeSH term(s) | Animals ; Cell Hypoxia/drug effects ; Cell Hypoxia/physiology ; Gene Silencing ; Glucose/pharmacology ; HEK293 Cells ; Hippocampus/cytology ; Hippocampus/metabolism ; Humans ; Ion Transport/drug effects ; Ion Transport/physiology ; Magnesium/metabolism ; Neurons/cytology ; Neurons/metabolism ; Protein-Serine-Threonine Kinases ; Rats ; Sweetening Agents ; TRPM Cation Channels/biosynthesis ; TRPM Cation Channels/genetics | |||||
| Chemical Substances | Sweetening Agents ; TRPM Cation Channels ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1) ; Trpm7 protein, rat (EC 2.7.11.1) ; Magnesium (I38ZP9992A) ; Glucose (IY9XDZ35W2) | |||||
| Language | English | |||||
| Publishing date | 2011-04-12 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 2997-x | |||||
| ISSN | 1083-351X ; 0021-9258 | |||||
| ISSN (online) | 1083-351X | |||||
| ISSN | 0021-9258 | |||||
| DOI | 10.1074/jbc.M110.148494 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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