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In this report we describe our studies on intracellular signals that mediate neurite outgrowth and long-term survival of cerebellar granule cells. The effect of voltage-gated calcium channel activation on neurite complexity was evaluated in cultured cerebellar granule cells grown for 48 h at low density; the parameter measured was the fractal dimension of the cell. We explored the contribution of two intracellular pathways, Ca2+ calmodulin-dependent protein kinase II and mitogen-activated protein kinase kinase (MEK1), to the effects of high [K+]e under serum-free conditions. We found that 25 mM KCI (25K) induced an increase in calcium influx through L subtype channels. In neurones grown for 24-48 h under low-density conditions, the activation of these channels induced neurite outgrowth through the activation of Ca2+ calmodulin-dependent protein kinase II. This also produced an increase in long-term neuronal survival with a partial contribution from the MEK1 pathway. We also found that the addition of 25K increased the levels of the phosphorylated forms of Ca2+ calmodulin-dependent protein kinase II and of the extracellular signal-regulated kinases 1 and 2. Neuronal survival under resting conditions is supported by the MEK1 pathway. We conclude that intracellular calcium oscillations can triggered different biological effects depending on the stage of maturation of the neuronal phenotype. Ca2+ calmodulin-dependent protein kinase II activation determines the growth of neurites and the development of neuronal complexity.


Documento: Artículo
Título:Contribution of Ca2+ calmodulin-dependent protein kinase II and mitogen-activated protein kinase kinase to neural activity-induced neurite outgrowth and survival of cerebellar granule cells
Autor:Borodinsky, L.N.; Coso, O.A.; Fiszman, M.L.
Filiación:Instituto de Investigaciones Farmacológicas, CONICET, Buenos Aires, Argentina
Laboratorio de Fisiología y Biología Molecular, FCEyN, UBA, Buenos Aires, Argentina
ININFA-CONICET, Junín 956, 1113 Buenos Aires, Argentina
Palabras clave:CaMKII and MEK1 pathways; Cerebellar granule cells; Fractal dimension; Neural activity; Neurite outgrowth; Neuronal survival; calcium channel; calcium ion; mitogen activated protein kinase 1; mitogen activated protein kinase kinase; potassium chloride; protein kinase (calcium,calmodulin) II; calcium; calcium channel; calcium channel blocking agent; calmodulin dependent protein kinase ii; calmodulin-dependent protein kinase II; enzyme inhibitor; mitogen activated protein kinase; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase kinase; mitogen activated protein kinase kinase 1; protein kinase (calcium,calmodulin); protein serine threonine kinase; animal cell; article; calcium cell level; calcium signaling; calcium transport; cell survival; controlled study; fractal analysis; granule cell; nerve fiber growth; nonhuman; phenotype; priority journal; rat; signal transduction; animal; cell culture; cell differentiation; cell survival; cerebellum; culture medium; cytology; drug antagonism; drug effect; enzyme activation; enzymology; metabolism; nerve cell; neurite; physiology; Sprague Dawley rat; time; Animalia; Animals; Ca(2+)-Calmodulin Dependent Protein Kinase; Calcium; Calcium Channel Blockers; Calcium Channels; Cell Differentiation; Cell Survival; Cells, Cultured; Cerebellum; Culture Media, Serum-Free; Enzyme Activation; Enzyme Inhibitors; MAP Kinase Kinase 1; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Neurites; Neurons; Protein-Serine-Threonine Kinases; Rats; Rats, Sprague-Dawley; Signal Transduction; Time Factors
Página de inicio:1062
Página de fin:1070
Título revista:Journal of Neurochemistry
Título revista abreviado:J. Neurochem.
CAS:Ca(2+)-Calmodulin Dependent Protein Kinase, EC; Calcium Channel Blockers; Calcium Channels; Calcium, 7440-70-2; calmodulin-dependent protein kinase II, EC; Culture Media, Serum-Free; Enzyme Inhibitors; MAP Kinase Kinase 1, EC 2.7.1.-; Mitogen-Activated Protein Kinase 1, EC; Mitogen-Activated Protein Kinase 3, EC; Mitogen-Activated Protein Kinase Kinases, EC 2.7.1.-; Mitogen-Activated Protein Kinases, EC; Protein-Serine-Threonine Kinases, EC


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---------- APA ----------
Borodinsky, L.N., Coso, O.A. & Fiszman, M.L. (2002) . Contribution of Ca2+ calmodulin-dependent protein kinase II and mitogen-activated protein kinase kinase to neural activity-induced neurite outgrowth and survival of cerebellar granule cells. Journal of Neurochemistry, 80(6), 1062-1070.
---------- CHICAGO ----------
Borodinsky, L.N., Coso, O.A., Fiszman, M.L. "Contribution of Ca2+ calmodulin-dependent protein kinase II and mitogen-activated protein kinase kinase to neural activity-induced neurite outgrowth and survival of cerebellar granule cells" . Journal of Neurochemistry 80, no. 6 (2002) : 1062-1070.
---------- MLA ----------
Borodinsky, L.N., Coso, O.A., Fiszman, M.L. "Contribution of Ca2+ calmodulin-dependent protein kinase II and mitogen-activated protein kinase kinase to neural activity-induced neurite outgrowth and survival of cerebellar granule cells" . Journal of Neurochemistry, vol. 80, no. 6, 2002, pp. 1062-1070.
---------- VANCOUVER ----------
Borodinsky, L.N., Coso, O.A., Fiszman, M.L. Contribution of Ca2+ calmodulin-dependent protein kinase II and mitogen-activated protein kinase kinase to neural activity-induced neurite outgrowth and survival of cerebellar granule cells. J. Neurochem. 2002;80(6):1062-1070.