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Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Brain+Res 2011 ; 1369 (ä): 21-35 Nephropedia Template TP
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Mg2+ ions reduce microglial and THP-1 cell neurotoxicity by inhibiting Ca2+ entry through purinergic channels #MMPMID21040713
Lee M; Jantaratnotai N; McGeer E; McLarnon JG; McGeer PL
Brain Res 2011[Jan]; 1369 (ä): 21-35 PMID21040713show ga
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 NFkappaB. This caused release of TNFalpha, 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.