Department of Otorinolaringoiatria, Audiologia and Foniatria G. Ferreri, Policlinico Umberto I, Rome, Italy.
J Cell Biochem. 2010 Apr 1;109(5):1006-12. doi: 10.1002/jcb.22480.
Signal transduction pathways, involved in cell cycle and activities, depend on various components including lipid signalling molecules, such as phosphoinositides and related enzymes. Many evidences support the hypothesis that inositol lipid cycle is involved in astrocytes activation during neurodegeneration. Previous studies investigated the pattern of expression of phosphoinositide-specific phospholipase C (PI-PLC) family isoforms in astrocytes, individuating in cultured neonatal rat astrocytes, supposed to be quiescent cells, the absence of some isoforms, accordingly to their well known tissue specificity. The same study was conducted in cultured rat astrocytoma C6 cells and designed a different pattern of expression of PI-PLCs in the neoplastic counterpart, accordingly to literature suggesting a PI signalling involvement in tumour progression. It is not clear the role of PI-PLC isoforms in inflammation; recent data demonstrate they are involved in cytokines production, with special regard to IL-6. PI-PLCs expression in LPS treated neonatal rat astrocytes performed by using RT-PCR, observed at 3, 6, 18 and 24 h intervals, expressed: PI-PLC beta1, beta4 and gamma1 in all intervals analysed; PI-PLC delta1 at 6, 18 and 24 h; PI-PLC delta3 at 6 h after treatment. PI-PLC beta3, delta4 and epsilon, present in untreated astrocytes, were not detected after LPS treatment. Immunocytochemical analysis, performed to visualize the sub-cellular distribution of the expressed isoforms, demonstrated different patterns of localisation at different times of exposure. These observations suggest that PI-PLCs expression and distribution may play a role in ongoing inflammation process of CNS.
细胞信号转导通路涉及细胞周期和活动,依赖于各种成分,包括脂质信号分子,如磷酸肌醇和相关酶。许多证据支持这样一种假设,即肌醇脂质循环参与神经退行性变期间星形胶质细胞的激活。先前的研究调查了磷酸肌醇特异性磷脂酶 C(PI-PLC)家族同工型在星形胶质细胞中的表达模式,在培养的新生大鼠星形胶质细胞中鉴定出一些同工型缺失,根据它们已知的组织特异性。在培养的大鼠星形细胞瘤 C6 细胞中进行了相同的研究,设计了 PI-PLC 在肿瘤对应物中的不同表达模式,根据文献表明 PI 信号参与肿瘤进展。PI-PLC 同工型在炎症中的作用尚不清楚;最近的数据表明它们参与细胞因子的产生,特别是白细胞介素 6。使用 RT-PCR 观察到 LPS 处理的新生大鼠星形胶质细胞中 PI-PLCs 的表达:PI-PLC beta1、beta4 和 gamma1 在所有分析的时间间隔内表达;PI-PLC delta1 在 6、18 和 24 小时;PI-PLC delta3 在处理后 6 小时。PI-PLC beta3、delta4 和 epsilon 在未处理的星形胶质细胞中存在,但在 LPS 处理后未检测到。免疫细胞化学分析用于可视化表达同工型的亚细胞分布,显示出不同的定位模式在不同的暴露时间。这些观察结果表明,PI-PLCs 的表达和分布可能在中枢神经系统的持续炎症过程中发挥作用。