RRC ID 68450
Author Koshimura K, Murakami Y, Sohmiya M, Tanaka J, Kato Y.
Title Effects of erythropoietin on neuronal activity.
Journal J Neurochem
Abstract Recently, erythropoietin (EPO) receptors and synthesis of EPO have been identified in the brain. To clarify the effects of EPO on neuronal cells, we investigated the effects of EPO on Ca2+ uptake, intracellular Ca2+ concentration, membrane potential, cell survival, release and biosynthesis of dopamine, and nitric oxide (NO) production in differentiated PC12 cells, which possess EPO receptors. EPO (10(-12)-10(-10) M) increased 45Ca2+ uptake and intracellular Ca2+ concentration in PC12 cells in a dose-related manner; these increases were inhibited by nicardipine (1 microM) or anti-EPO antibody (1:100 dilution). EPO induced membrane depolarization in PC12 cells. After a 5-day culture without serum and nerve growth factor (NGF), viable cell number decreased to 50% of that of the control cells cultured with serum and NGF. EPO (10(-13)-10(-10) M) increased the number of viable cells cultured without serum and NGF; this increase was blunted by nicardipine or anti-EPO antibody. Incubation with EPO (10(-13)-10(-10) M) stimulated mitogen-activated protein kinase activity in PC12 cells. EPO (10(-13)-10(-10) M) increased dopamine release from PC12 cells and tyrosine hydroxylase activity; these increases were sensitive to nicardipine or anti-EPO antibody. Following a 4-h incubation with EPO (10(-14)-10(-10) M), NO production was increased, which was blunted by nicardipine and anti-EPO antibody. In contrast, maximal NO synthase activity was not changed by EPO. These results suggest that EPO stimulates neuronal function and viability via activation of Ca2+ channels.
Volume 72(6)
Pages 2565-72
Published 1999-6-1
DOI 10.1046/j.1471-4159.1999.0722565.x
PMID 10349868
MeSH Animals Antibodies / pharmacology Biological Transport Calcium / metabolism* Calcium-Calmodulin-Dependent Protein Kinases / metabolism Cell Differentiation / drug effects Cell Membrane / drug effects Cell Membrane / physiology* Cell Survival / drug effects Dopamine / metabolism Erythropoietin / immunology Erythropoietin / pharmacology* Humans Membrane Potentials / drug effects Membrane Potentials / physiology Nerve Growth Factors / pharmacology Neurons / cytology Neurons / drug effects Neurons / physiology* Nicardipine / pharmacology Nitric Oxide / metabolism PC12 Cells Rats Recombinant Proteins Tyrosine 3-Monooxygenase / metabolism
IF 4.066
Human and Animal Cells PC-12(RCB0009)