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The activation of MEK-ERK1/2 by glutamate receptor-stimulation is involved in the regulation of RPE proliferation and morphologic transformation.
Exp Eye Res. 2008 Feb; 86(2):207-19.EE

Abstract

Retinal pigment epithelial (RPE) cells are the main cell type involved in the pathogenesis of proliferative vitreoretinopathy (PVR). As a result from retinal detachment or surgical procedures, RPE comes in contact with glutamate from serum, glial release and the injured retina. The purpose of this study was to explore a possible role for glutamate in the development of PVR, mediated by the receptor-stimulated activation of the ERK1/2 MAPK pathway, the alteration of cell proliferation and the transdifferentiation of RPE cells, using rat RPE cells in culture as a model system. We demonstrated the expression in these cells of Group I metabotropic-and ionotropic AMPA/KA and NMDA glutamate receptors (GluRs), predominantly of the NMDA subtype, which are targeted to the membrane, and exhibit pharmacological and biochemical characteristics equivalent to those previously established in brain tissue. Proliferation was measured by MTS-reduction colorimetric assay, and actin cytoskeleton dynamics was visualized by immunoflurescence using alpha-sma specific antibodies. Activation of metabotropic, AMPA and NMDA receptors by glutamate induced the time-and dose-dependent phosphorylation of ERK1/2, assessed by Western blot analysis, in parallel to a significant increase in cell proliferation and a decrease in alpha-sma expression and its recruitment into stress fibers. These effects were all prevented by the inhibition of MEK. Hence, results suggest that glutamate could be involved in the generation of PVR, through a GluR-mediated increase in proliferation and phenotypic transformation, cause-effect related to the activation of ERK1/2.

Authors+Show Affiliations

Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), México, DF, Mexico.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18061165

Citation

Pacheco-Domínguez, Reyna Lizette, et al. "The Activation of MEK-ERK1/2 By Glutamate Receptor-stimulation Is Involved in the Regulation of RPE Proliferation and Morphologic Transformation." Experimental Eye Research, vol. 86, no. 2, 2008, pp. 207-19.
Pacheco-Domínguez RL, Palma-Nicolas JP, López E, et al. The activation of MEK-ERK1/2 by glutamate receptor-stimulation is involved in the regulation of RPE proliferation and morphologic transformation. Exp Eye Res. 2008;86(2):207-19.
Pacheco-Domínguez, R. L., Palma-Nicolas, J. P., López, E., & López-Colomé, A. M. (2008). The activation of MEK-ERK1/2 by glutamate receptor-stimulation is involved in the regulation of RPE proliferation and morphologic transformation. Experimental Eye Research, 86(2), 207-19.
Pacheco-Domínguez RL, et al. The Activation of MEK-ERK1/2 By Glutamate Receptor-stimulation Is Involved in the Regulation of RPE Proliferation and Morphologic Transformation. Exp Eye Res. 2008;86(2):207-19. PubMed PMID: 18061165.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The activation of MEK-ERK1/2 by glutamate receptor-stimulation is involved in the regulation of RPE proliferation and morphologic transformation. AU - Pacheco-Domínguez,Reyna Lizette, AU - Palma-Nicolas,J Prisco, AU - López,Edith, AU - López-Colomé,Ana María, Y1 - 2007/10/30/ PY - 2007/06/30/received PY - 2007/10/15/revised PY - 2007/10/18/accepted PY - 2007/12/7/pubmed PY - 2008/4/17/medline PY - 2007/12/7/entrez SP - 207 EP - 19 JF - Experimental eye research JO - Exp. Eye Res. VL - 86 IS - 2 N2 - Retinal pigment epithelial (RPE) cells are the main cell type involved in the pathogenesis of proliferative vitreoretinopathy (PVR). As a result from retinal detachment or surgical procedures, RPE comes in contact with glutamate from serum, glial release and the injured retina. The purpose of this study was to explore a possible role for glutamate in the development of PVR, mediated by the receptor-stimulated activation of the ERK1/2 MAPK pathway, the alteration of cell proliferation and the transdifferentiation of RPE cells, using rat RPE cells in culture as a model system. We demonstrated the expression in these cells of Group I metabotropic-and ionotropic AMPA/KA and NMDA glutamate receptors (GluRs), predominantly of the NMDA subtype, which are targeted to the membrane, and exhibit pharmacological and biochemical characteristics equivalent to those previously established in brain tissue. Proliferation was measured by MTS-reduction colorimetric assay, and actin cytoskeleton dynamics was visualized by immunoflurescence using alpha-sma specific antibodies. Activation of metabotropic, AMPA and NMDA receptors by glutamate induced the time-and dose-dependent phosphorylation of ERK1/2, assessed by Western blot analysis, in parallel to a significant increase in cell proliferation and a decrease in alpha-sma expression and its recruitment into stress fibers. These effects were all prevented by the inhibition of MEK. Hence, results suggest that glutamate could be involved in the generation of PVR, through a GluR-mediated increase in proliferation and phenotypic transformation, cause-effect related to the activation of ERK1/2. SN - 0014-4835 UR - https://www.unboundmedicine.com/medline/citation/18061165/The_activation_of_MEK_ERK1/2_by_glutamate_receptor_stimulation_is_involved_in_the_regulation_of_RPE_proliferation_and_morphologic_transformation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(07)00304-1 DB - PRIME DP - Unbound Medicine ER -