Cechin Sirlene R, Dunkley Peter R, Rodnight Richard
School of Biomedical Sciences and the Hunter Medical Research Institute, University of Newcastle, 2308, Callaghan, NSW, Australia.
Neurochem Res. 2005 May;30(5):603-11. doi: 10.1007/s11064-005-2747-4.
We studied pathways involved in the proliferation of rat C6 glioma cells induced by lysophosphatidic acid (LPA), a phospholipid with diverse biological functions. LPA induced a dose-responsive proliferation of C6 cells after 48 h. Proliferation was blocked by inhibitors of the sodium/proton exchanger type 1 (NHE1), Rho-associated kinase, the phosphatidylinositol 3-kinase/Akt pathway (PI3K/Akt), protein kinase C (PKC) and extracellular signal regulated kinase kinase (MEK). Phospho-specific antibodies were used to investigate the pathways involved. LPA induced transient (10 min) phosphorylations of ERK 1/2, Akt and the transcription factor CREB. The LPA-induced phosphorylation of ERK 1/2 and CREB was blocked by inhibition of PI3K, PKC and MEK, but that of Akt was only inhibited by wortmannin, the PI3K inhibitor. Inhibition of Rho kinase or NHE1 did not reduce the LPA-induced phosphorylation of ERK, Akt or CREB. The results were compared with the effects of LPA on transduction pathways in other cell types.
我们研究了溶血磷脂酸（LPA，一种具有多种生物学功能的磷脂）诱导大鼠C6胶质瘤细胞增殖所涉及的信号通路。48小时后，LPA诱导C6细胞呈剂量依赖性增殖。钠/质子交换体1型（NHE1）抑制剂、Rho相关激酶抑制剂、磷脂酰肌醇3激酶/Akt信号通路（PI3K/Akt）抑制剂、蛋白激酶C（PKC）抑制剂和细胞外信号调节激酶激酶（MEK）抑制剂均可阻断细胞增殖。使用磷酸化特异性抗体研究相关信号通路。LPA诱导细胞外信号调节激酶1/2（ERK 1/2）、Akt和转录因子CREB短暂（10分钟）磷酸化。PI3K、PKC和MEK的抑制可阻断LPA诱导的ERK 1/2和CREB磷酸化，但Akt的磷酸化仅被PI3K抑制剂渥曼青霉素抑制。Rho激酶或NHE1的抑制并未降低LPA诱导的ERK、Akt或CREB磷酸化。将这些结果与LPA对其他细胞类型信号转导通路的影响进行了比较。
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