Effect of 1-oleoyl-2-acetyl-sn-glycerol on inositol lipid metabolism of ascites tumor cells in culture.

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.

• Authors: J B Strosznajder, E W Haeffner
• Journal: Journal of lipid mediators (J Lipid Mediat) 1989 May-Jun Vol. 1 Issue 3 Pg. 175-87 ISSN: 0921-8319 [Print] Netherlands
• PMID: 2562433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diglycerides
• Inositol Phosphates
• Purine Nucleotides
• 1-oleoyl-2-acetylglycerol
• Phosphotransferases
• Phosphotransferases (Alcohol Group Acceptor)
• 1-Phosphatidylinositol 4-Kinase
• 1-phosphatidylinositol-4-phosphate 5-kinase
• Type C Phospholipases

Topics

• 1-Phosphatidylinositol 4-Kinase
• Animals
• Carcinoma, Ehrlich Tumor (metabolism)
• Cell Membrane (enzymology)
• Diglycerides (pharmacology)
• Inositol Phosphates (metabolism)
• Phosphotransferases (metabolism)
• Phosphotransferases (Alcohol Group Acceptor)
• Purine Nucleotides (pharmacology)
• Second Messenger Systems (drug effects, physiology)
• Tumor Cells, Cultured (drug effects, metabolism)
• Type C Phospholipases (metabolism)