pH is an intracellular effector controlling differentiation of oligodendrocyte precursors in culture via activation of the ERK1/2 pathway.
We reported previously that onset of oligodendrocyte precursor cell (OPC) differentiation is accompanied by an increase in intracellular pH (pH(i)). We show that OPC differentiation is dependent primarily on a permissive pH(i) value. The highest differentiation levels were observed for pH(i) values around 7.15 and inhibition of differentiation was observed at slightly more acidic or alkaline values. Clamping the pH(i) of OPCs at 7.15 caused a transient activation of ERK1/2 that was not observed at more acidic or alkaline values. Furthermore, inhibition of ERK activation with the UO126 compound totally prevented OPC differentiation in response to pH(i) shift. These results indicate that pH(i), acting through the ERK1/2 pathway, is a key determinant for oligodendrocyte differentiation. We also show that this pH(i) pathway is involved in the process of retinoic acid-induced OPC differentiation.
Bernard
Frédéric
F
Inserm U 575, Physiopathologie du Système Nerveux, IFR des Neurosciences, Strasbourg, France.
Vanhoutte
Peter
P
Bennasroune
Amar
A
Labourdette
Gérard
G
Perraut
Martine
M
Aunis
Dominique
D
Gaillard
Stéphane
S
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D045604:Extracellular Fluid / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry / Q000379:methods; D020935:MAP Kinase Signaling System / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D009844:Oligosaccharides / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
D002070:Butadienes; D004791:Enzyme Inhibitors; D005732:Gangliosides; D009419:Nerve Tissue Proteins; D009570:Nitriles; D009844:Oligosaccharides; C113580:U 0126; C062875:ganglioside A2B5; D014212:Tretinoin; D048052:Mitogen-Activated Protein Kinase 3