Marmiroli S, Ognibene A, Bavelloni A, Cinti C, Cocco L, Maraldi N M
Istituto di Citomorfologia Normale e Patologica, Consiglio Nazionale delle Richerche, Bologna, Italy.
J Biol Chem. 1994 Jan 7;269(1):13-6.
Interleukin 1 (IL-1) is one of the most potent stimulators of bone resorption. However, the early biochemical events elicited by IL-1 receptor binding are not fully understood. Here we show that in human osteosarcoma SaOS-2 cells the treatment with IL-1 alpha is able to evoke a rapid and transient increase of nuclear phospholipase C (PLC) activity. A parallel decrease of nuclear phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate is observed. All these events are strictly confined to the nuclear compartment without affecting the cytoplasmatic inositol lipid pool. In addition we show that by Western blot analysis with specific monoclonal antibodies the PLC gamma is located both in the cytoplasm and in the nucleus, while PLC beta appears exclusively localized in the nucleus. Moreover, the increase of PLC activity in response to IL-1 alpha is completely neutralized by monoclonal antibody against the beta-form. While confirming the existence of an autonomous nuclear phosphoinositide signaling system, our data clearly indicate that in SaOS-2 cells one of the earliest events following IL-1 alpha treatment is the breakdown of nuclear phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate because of the activation of a specific nuclear PLC isoform.
白细胞介素1（IL-1）是骨吸收最有效的刺激因子之一。然而，IL-1受体结合引发的早期生化事件尚未完全明了。在此我们表明，在人骨肉瘤SaOS-2细胞中，用IL-1α处理能够引起核磷脂酶C（PLC）活性快速短暂增加。同时观察到核磷脂酰肌醇单磷酸和磷脂酰肌醇二磷酸平行减少。所有这些事件都严格局限于核区室，而不影响细胞质肌醇脂质池。此外，我们通过用特异性单克隆抗体进行蛋白质印迹分析表明，PLCγ定位于细胞质和细胞核，而PLCβ仅定位于细胞核。而且，针对β形式的单克隆抗体完全中和了IL-1α刺激引起的PLC活性增加。在证实存在自主核磷酸肌醇信号系统的同时，我们的数据清楚地表明，在SaOS-2细胞中，IL-1α处理后最早发生的事件之一是由于特定核PLC同工型的激活导致核磷脂酰肌醇单磷酸和磷脂酰肌醇二磷酸的分解。
