Activation of phospholipase D participates in signal transduction pathways responsive to gamma-radiation.
Early responses of mammalian cells to ionizing radiation include the activation of a protein kinase C implicated in the regulation of gene expression, the stimulation of tyrosine kinase activities, and the enhancement of phosphatidylinositol turnover. In the present report we show that clinically relevant doses of gamma-radiation (2 Gy) stimulate phosphatidylcholine hydrolysis in human squamous carcinoma cells. Radiation induced the accumulation of intracellular [3H]choline and the simultaneous increase in [3H]myristoyl-phosphatidic acid, followed by a small increase in the levels of [3H]myristoyl-diacylglycerol. Furthermore, in the presence of ethanol, gamma-radiation stimulated the appearance of [32P]phosphatidylethanol, an indicator of phospholipase D transphosphatidylation activity. These data demonstrate for the first time that phospholipase D activation participates in signaling pathways in response to gamma-radiation.
Avila
M A
MA
Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20007.
Otero
G
G
Cansado
J
J
Dritschilo
A
A
Velasco
J A
JA
Notario
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V
D002294:Carcinoma, Squamous Cell; D002794:Choline / Q000378:metabolism; D004789:Enzyme Activation; D005720:Gamma Rays; D020404:Glycerophospholipids; D005997:Glycerylphosphorylcholine / Q000378:metabolism; D006258:Head and Neck Neoplasms; D006801:Humans; D007700:Kinetics; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism* / Q000528:radiation effects; D010767:Phosphorylcholine / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects*; D014407:Tumor Cells, Cultured
D020404:Glycerophospholipids; D009227:Myristic Acids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; C051521:phosphatidylethanol; D019814:Myristic Acid; D010767:Phosphorylcholine; D005997:Glycerylphosphorylcholine; D010739:Phospholipase D; D002794:Choline