Journal
EUROPEAN JOURNAL OF CANCER
Volume 38, Issue 18, Pages 2463-2475Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0959-8049(02)00485-9
Keywords
glycerophosphoinositol; phosphoinositides; inositol phosphates; Ras transformation; liquid chromatography-tandem mass spectrometry; phosphatidylinositol 4,5-bisphosphate
Categories
Funding
- Telethon [E.0841] Funding Source: Medline
Ask authors/readers for more resources
Inositol-containing molecules are involved in important cellular functions, including signalling, membrane transport and secretion. Our interest is in lysophosphatidylinositol and the glycerophosphoinositols, which modulate cell proliferation and G-protein-dependent activities such as adenylyl cyclase and phospholipase A(2). To investigate the role of glycerophosphoinositol (GroPIns) in the modulation of Ras-dependent pathways and its correlation to Ras transformation, we employed a novel liquid chromatography-tandem mass spectrometry technique to directly measure GroPIns in cell extracts. The cellular levels of GroPIns in selected parental and Ras-transformed cells, and in some carcinoma cells, ranged from 44 to 925 muM, with no consistent correlation to Ras transformation across all cell lines. Moreover, the derived cellular inositol concentrations revealed a wide range (similar to150 muM to similar to100 mM) under standard [H-3]-inositol-loading, suggesting a complex relationship between the inositol pool and the phosphoinositides and their derivatives. We have investigated these pools under specific loading conditions, designing a further HPLC analysis for GroPIns, combined with mass determinations of cellular phosphatidylinositol 4,5-bisphosphate. The data demonstrate that limiting inositol conditions identify a preferred pathway of inositol incorporation and retention into the polyphosphoinositides pool. Thus, under conditions of increased metabolic activity, such as receptor stimulation or cellular transformation, the polyphosphoinositide levels will be maintained at the expense of phosphatidylinositol and the turnover of its aqueous derivatives. (C) 2002 Elsevier Science Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available