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.

译文

我们以前曾报道过少突胶质细胞前体细胞 (OPC) 分化的开始伴随着细胞内pH(i)) 的增加。我们表明OPC的分化主要取决于允许的pH(i) 值。对于7.15附近的pH(i) 值观察到最高的分化水平,并且在稍微更酸性或碱性值观察到分化的抑制。将OPCs的pH(i) 夹在7.15引起ERK1/2的瞬时活化,这在更酸性或碱性值下没有观察到。此外,用UO126化合物抑制ERK活化完全阻止了响应pH(i) 位移的OPC分化。这些结果表明,pH(i) 通过ERK1/2途径起作用,是少突胶质细胞分化的关键决定因素。我们还表明,该pH(i) 途径参与了视黄酸诱导的OPC分化过程。

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