Mg2+ ions reduce microglial and THP-1 cell neurotoxicity by inhibiting Ca2+ entry through purinergic channels.
Identifieur interne : 001638 ( Main/Exploration ); précédent : 001637; suivant : 001639Mg2+ ions reduce microglial and THP-1 cell neurotoxicity by inhibiting Ca2+ entry through purinergic channels.
Auteurs : Moonhee Lee [Canada] ; Nattinee Jantaratnotai ; Edith Mcgeer ; James G. Mclarnon ; Patrick L. McgeerSource :
- Brain research [ 1872-6240 ] ; 2011.
English descriptors
- KwdEn :
- Blotting, Western, Calcium (metabolism), Cell Line, Humans, Inflammation (metabolism), Inflammation (pathology), Inflammation (physiopathology), Interleukin-6 (biosynthesis), Ions (metabolism), Magnesium (metabolism), Microglia (drug effects), Microglia (metabolism), Microglia (pathology), Purinergic Agonists (pharmacology), Receptors, Purinergic P2 (metabolism), Receptors, Purinergic P2X7 (metabolism), Receptors, Purinergic P2Y2 (metabolism), Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction (physiology), Tumor Necrosis Factor-alpha (biosynthesis).
- MESH :
- chemical , biosynthesis : Interleukin-6, Tumor Necrosis Factor-alpha.
- chemical , metabolism : Calcium, Ions, Magnesium, Receptors, Purinergic P2, Receptors, Purinergic P2X7, Receptors, Purinergic P2Y2.
- drug effects : Microglia.
- metabolism : Inflammation, Microglia.
- pathology : Inflammation, Microglia.
- chemical , pharmacology : Purinergic Agonists.
- physiology : Signal Transduction.
- physiopathology : Inflammation.
- Blotting, Western, Cell Line, Humans, Reverse Transcriptase Polymerase Chain Reaction.
Abstract
Mg(2+) is a known antagonist of some Ca(2+) ion channels. It may therefore be able to counteract the toxic consequences of excessive Ca(2+) entry into immune-type cells. Here we examined the effects of Mg(2+) on inflammation induced by Ca(2+) influx into microglia and THP-1 cells following activation of purinergic receptors. Using tissue culture, an inflammatory response was induced by treatment with either the P2X7 purinergic receptor agonist 2',3'-[benzoyl-4-benzoyl]-ATP (BzATP) or the P2Y2,4 receptor agonist uridine 5'-triphosphate (UTP). Both microglia and THP-1 cells expressed the mRNAs for these receptors. Treatment produced a rapid rise in intracellular Ca(2+) which was significantly reduced by Mg(2+) or the calcium chelator BAPTA-AM. Purinergic receptor stimulation activated the intracellular inflammatory pathway P38 MAP kinase and NFκB. This caused release of TNFα, IL-6, nitrite ions and other materials that are neurotoxic to SH-SY5Y cells. These effects were all ameliorated by Mg(2+). They were also partly ameliorated by the P2X7R antagonists, oxATP and KN-62, the P2YR antagonist MRS2179, and the store operated Ca(2+) channel blocker, SK96365. These results indicate that elevated Mg(2+) is a broad spectrum inhibitor of Ca(2+) entry into microglia or THP-1 cells. Mg(2+) administration may be a strategy for reducing the damaging consequences Ca(2+) induced neuroinflammation in degenerative neurological disorders such as Alzheimer disease and Parkinson disease.
DOI: 10.1016/j.brainres.2010.10.084
PubMed: 21040713
Affiliations:
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Mclarnon</name></author><author><name sortKey="Mcgeer, Patrick L" sort="Mcgeer, Patrick L" uniqKey="Mcgeer P" first="Patrick L" last="Mcgeer">Patrick L. Mcgeer</name></author></analytic><series><title level="j">Brain research</title><idno type="eISSN">1872-6240</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Blotting, Western</term><term>Calcium (metabolism)</term><term>Cell Line</term><term>Humans</term><term>Inflammation (metabolism)</term><term>Inflammation (pathology)</term><term>Inflammation (physiopathology)</term><term>Interleukin-6 (biosynthesis)</term><term>Ions (metabolism)</term><term>Magnesium (metabolism)</term><term>Microglia (drug effects)</term><term>Microglia (metabolism)</term><term>Microglia (pathology)</term><term>Purinergic Agonists (pharmacology)</term><term>Receptors, Purinergic P2 (metabolism)</term><term>Receptors, Purinergic P2X7 (metabolism)</term><term>Receptors, Purinergic P2Y2 (metabolism)</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Signal Transduction (physiology)</term><term>Tumor Necrosis Factor-alpha (biosynthesis)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Interleukin-6</term><term>Tumor Necrosis Factor-alpha</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calcium</term><term>Ions</term><term>Magnesium</term><term>Receptors, Purinergic P2</term><term>Receptors, Purinergic P2X7</term><term>Receptors, Purinergic P2Y2</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Microglia</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Inflammation</term><term>Microglia</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Inflammation</term><term>Microglia</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Purinergic Agonists</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Inflammation</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Blotting, Western</term><term>Cell Line</term><term>Humans</term><term>Reverse Transcriptase Polymerase Chain Reaction</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mg(2+) is a known antagonist of some Ca(2+) ion channels. It may therefore be able to counteract the toxic consequences of excessive Ca(2+) entry into immune-type cells. Here we examined the effects of Mg(2+) on inflammation induced by Ca(2+) influx into microglia and THP-1 cells following activation of purinergic receptors. Using tissue culture, an inflammatory response was induced by treatment with either the P2X7 purinergic receptor agonist 2',3'-[benzoyl-4-benzoyl]-ATP (BzATP) or the P2Y2,4 receptor agonist uridine 5'-triphosphate (UTP). Both microglia and THP-1 cells expressed the mRNAs for these receptors. Treatment produced a rapid rise in intracellular Ca(2+) which was significantly reduced by Mg(2+) or the calcium chelator BAPTA-AM. Purinergic receptor stimulation activated the intracellular inflammatory pathway P38 MAP kinase and NFκB. This caused release of TNFα, IL-6, nitrite ions and other materials that are neurotoxic to SH-SY5Y cells. These effects were all ameliorated by Mg(2+). They were also partly ameliorated by the P2X7R antagonists, oxATP and KN-62, the P2YR antagonist MRS2179, and the store operated Ca(2+) channel blocker, SK96365. These results indicate that elevated Mg(2+) is a broad spectrum inhibitor of Ca(2+) entry into microglia or THP-1 cells. Mg(2+) administration may be a strategy for reducing the damaging consequences Ca(2+) induced neuroinflammation in degenerative neurological disorders such as Alzheimer disease and Parkinson disease.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Jantaratnotai, Nattinee" sort="Jantaratnotai, Nattinee" uniqKey="Jantaratnotai N" first="Nattinee" last="Jantaratnotai">Nattinee Jantaratnotai</name><name sortKey="Mcgeer, Edith" sort="Mcgeer, Edith" uniqKey="Mcgeer E" first="Edith" last="Mcgeer">Edith Mcgeer</name><name sortKey="Mcgeer, Patrick L" sort="Mcgeer, Patrick L" uniqKey="Mcgeer P" first="Patrick L" last="Mcgeer">Patrick L. Mcgeer</name><name sortKey="Mclarnon, James G" sort="Mclarnon, James G" uniqKey="Mclarnon J" first="James G" last="Mclarnon">James G. Mclarnon</name></noCountry><country name="Canada"><noRegion><name sortKey="Lee, Moonhee" sort="Lee, Moonhee" uniqKey="Lee M" first="Moonhee" last="Lee">Moonhee Lee</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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