Strosznajder Jb, Haeffner Ew
May 1, 1989
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Influential Citations
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Quality indicators
Journal
Journal of lipid mediators
Abstract
1-Oleoyl-2-acetyl-sn-glycerol (OAG), the membrane-permeable analogue of 1,2-diacylglycerol (DAG), which stimulates ascites tumor cell proliferation, was used to study its effect on phosphoinositide metabolism. Culturing of ascites cells labeled with [3H]inositol at low serum concentration in the presence of OAG suppressed the radioactivity level of the inositol phosphates, particularly IP3. Membrane-bound, Ca(2+)- and GTP gamma S-sensitive PI- and PIP2-specific phosphodiesterase (phospholipase C) showed much lower activities in OAG-stimulated cells, which could be enhanced by GTP gamma S in these but not in the unstimulated cells. A high susceptibility to Ca2+ of the PI- and PIP2-specific phospholipase C of non-stimulated cells was observed. The PIP-kinase activity was similarly reduced by about 85% in OAG-stimulated cells. These data indicate a negative feedback regulation of the phosphoinositide metabolism mediated by OAG. Reduction in synthesis and degradation of PIP2, which furnishes the two second messengers, DAG and IP3, provides a means of controlling the intracellular level of these molecules, which is important for a balanced proliferation rate.