Lysophosphatidic acid possesses dual action in cell proliferation

Gabor Tigyi, David L. Dyer, Ricardo Miledi

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Abstract

Lysophosphatidic acid (LPA) induces mitogenic responses in cultured fibroblasts through a pertussis toxin-sensitive signaling pathway. In contrast, we have shown that LPA inhibits the proliferation of Sp2/0-Ag14 myeloma cells. To resolve this apparent controversy, LPA-elicited responses in cell proliferation and the underlying second messenger mechanisms were compared in Sp2/0-Ag14 myeloma and NIH 3T3 fibroblast cells. The antimitogenic response was not elicited by micromolar concentrations of phosphatidic acid, phosphatidylglycerol, or diacylglycerol. In NIH 3T3 and Sp2 cells, LPA elicited an increase in inositol trisphosphate and a subsequent transient increase in free cytoplasmic Ca2+. Unlike the mitogenic response in NIH 3T3 cells, the antimitogenic effect was not affected by pertussis toxin; on the contrary, it was accompanied by an increase in cAMP. In Sp2 cells, cAMP analogs, forskolin, and isobutylmethylxanthine inhibited cell proliferation and enhanced LPA action in an additive manner, suggesting that an LPA-elicited increase in cAMP- mediated signaling was responsible for the antimitogenic response. In addition to the mitogenic response in fibroblasts and the antimitogenic response in tumor cell lines, there are some cell types (Jurkat T-cell lymphoma and primary astrocytes) in which LPA is ineffective in altering cell proliferation. The cell-type-specific dual action of LPA suggests that this endogenous lipid mediator when released from activated cells might play an important role as a regulator, rather than a ubiquitous inducer, of cell proliferation.

Original languageEnglish (US)
Pages (from-to)1908-1912
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number5
DOIs
StatePublished - Mar 1 1994

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Cell Proliferation
NIH 3T3 Cells
Fibroblasts
Pertussis Toxin
Phosphatidylglycerols
Phosphatidic Acids
Jurkat Cells
lysophosphatidic acid
T-Cell Lymphoma
Diglycerides
Second Messenger Systems
Colforsin
Inositol
Helper-Inducer T-Lymphocytes
Tumor Cell Line
Astrocytes
Lipids

All Science Journal Classification (ASJC) codes

  • General

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Lysophosphatidic acid possesses dual action in cell proliferation. / Tigyi, Gabor; Dyer, David L.; Miledi, Ricardo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 5, 01.03.1994, p. 1908-1912.

Research output: Contribution to journalArticle

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