PMID- 24374786 OWN - NLM STAT- MEDLINE DCOM- 20150105 LR - 20211021 IS - 1590-3478 (Electronic) IS - 1590-1874 (Linking) VI - 35 IP - 6 DP - 2014 Jun TI - Activation of NMDA receptor of glutamate influences MMP-2 activity and proliferation of glioma cells. PG - 823-9 LID - 10.1007/s10072-013-1604-5 [doi] AB - Glioblastoma multiforme (GBM) is the most common malignant glioma, which has high proliferative rate and an extremely invasive phenotype. Major limitations in the effective treatment of malignant gliomas are the proliferation and infiltration into the surrounding brain tissue. Although studies have shown that various stimuli promote glioma cell proliferation and invasion, the underlying mechanisms remain largely unknown. Glioma cells secrete significant amount of glutamate into surrounding tissue and intracellular signaling is thought to be initiated upon glutamate-induced modulation of the ion channels in GBM cells. The objective of the study was to investigate the effect of activation of NMDA (N-methyl-D-aspartate) receptors of glutamate on gelatinase subfamily MMPs and on proliferation of glioma cells. U251MG and U87MG cell lines were maintained in Dulbecco's Modified Eagle's Medium. Proliferation assay was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a yellow tetrazole (MTT) assay. Matrix metalloproteinase (MMP)-2 and MMP-9 activity was investigated by gelatin zymography assay. We demonstrate that activated NMDA receptors (NMDAR) increased the activity of MMP-2 only in U251MG glioma cells at concentrations of 100 and 200 muM and increased the proliferation of both U87MG and U251MG glioma cells at concentrations of 50, 100, 150 and 200 muM. Inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly inhibited the effect of activation of NMDAR on MMP-2 activity and on proliferation. We conclude that NMDA receptor activation has role in activity of MMP-2 and proliferation of glioma cells. FAU - Ramaswamy, Palaniswamy AU - Ramaswamy P AD - Department of Neurochemistry, National Institute of Mental Health and NeuroSciences (NIMHANS), Bangalore, Karnataka, 560029, India. FAU - Aditi Devi, N AU - Aditi Devi N FAU - Hurmath Fathima, K AU - Hurmath Fathima K FAU - Dalavaikodihalli Nanjaiah, Nandakumar AU - Dalavaikodihalli Nanjaiah N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131229 PL - Italy TA - Neurol Sci JT - Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology JID - 100959175 RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) SB - IM MH - Brain Neoplasms/*metabolism MH - Cell Proliferation MH - Glioblastoma/*metabolism MH - Humans MH - Matrix Metalloproteinase 2/*metabolism MH - Receptors, N-Methyl-D-Aspartate/*metabolism MH - Tumor Cells, Cultured EDAT- 2014/01/01 06:00 MHDA- 2015/01/06 06:00 CRDT- 2013/12/31 06:00 PHST- 2013/08/05 00:00 [received] PHST- 2013/12/10 00:00 [accepted] PHST- 2013/12/31 06:00 [entrez] PHST- 2014/01/01 06:00 [pubmed] PHST- 2015/01/06 06:00 [medline] AID - 10.1007/s10072-013-1604-5 [doi] PST - ppublish SO - Neurol Sci. 2014 Jun;35(6):823-9. doi: 10.1007/s10072-013-1604-5. Epub 2013 Dec 29.