Soliven Betty, Ma Lan, Bae Hyun, Attali Bernard, Sobko Alexander, Iwase Tamaki
Department of Neurology and Committee on Neurobiology, The Brain Research Institute, University of Chicago, 5841 S. Maryland, Chicago, IL 60637, USA.
Am J Physiol Cell Physiol. 2003 Jan;284(1):C85-93. doi: 10.1152/ajpcell.00145.2002.
An increase in the expression of the delayed rectifier current (I(K)) has been shown to correlate with mitogenesis in many cell types. However, pathways involved in the upregulation of I(K) by growth factors in oligodendroglial progenitors (OPs) have not been well-elucidated. In this study, we found that treatment with platelet-derived growth factor (PDGF) and basic fibroblast growth factor but not ciliary neurotrophic factor resulted in increased I(K) density and upregulation of Kv1.5 and Kv1.6 mRNA transcripts. The effect of PDGF on I(K) was blocked by mimosine, a cell cycle inhibitor, and by genistein, a tyrosine kinase inhibitor. Using inhibitors of PDGF-activated pathways, we found that PDGF-induced upregulation of Kv1.5 and I(K) density involves Src family tyrosine kinases, sphingosine kinase, and intracellular Ca(2+) but not ERK1/2 or phosphatidylinositol 3-kinase pathways. Furthermore, agents that were effective inhibitors of PDGF-induced I(K) upregulation also attenuated OP proliferation, supporting the concept that I(K) is an important link between PDGF-activated signaling cascades and cell cycle progression.
在许多细胞类型中，延迟整流电流（I(K)）表达的增加已被证明与有丝分裂相关。然而，少突胶质前体细胞（OPs）中生长因子上调I(K)所涉及的信号通路尚未得到充分阐明。在本研究中，我们发现血小板衍生生长因子（PDGF）和碱性成纤维细胞生长因子处理可导致I(K)密度增加以及Kv1.5和Kv1.6 mRNA转录本上调，而睫状神经营养因子处理则无此作用。细胞周期抑制剂含羞草碱和酪氨酸激酶抑制剂染料木黄酮可阻断PDGF对I(K)的作用。使用PDGF激活通路的抑制剂，我们发现PDGF诱导的Kv1.5上调和I(K)密度增加涉及Src家族酪氨酸激酶、鞘氨醇激酶和细胞内Ca(2+)，但不涉及ERK1/2或磷脂酰肌醇3激酶通路。此外，有效抑制PDGF诱导的I(K)上调的试剂也减弱了OP的增殖，这支持了I(K)是PDGF激活的信号级联反应与细胞周期进程之间重要联系的观点。
