The mechanism of sphingosine enhancement of phorbol ester-mediated phospholipase D activation in lymphocytes.
Tumor-promoting phorbol esters stimulate the production of phosphatidylethanol (PEt) in bovine lymph node lymphocytes through the activation of Phospholipase D (PLD). Sphingosine enhanced the 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated formation of PEt in lymphocytes, while it had no effect by itself. Interestingly, the incorporation of labeled arachidonic acid into phospholipids was increased by sphingosine. Examination of the effect of sphingosine along with TPA on the incorporation of [1-14C]labeled-arachidonic acid into individual phospholipids revealed that they enhanced significantly the specific activity of only PC and lyso-PC fractions. These observations indicate that sphingosine does not activate PLD directly as TPA does. It appears that sphingosine increases the specific radioactivity of the substrate pool for PLD which results in an apparent increase in PEt when both sphingosine and TPA are present.
Cao
Y Z
YZ
Department of Veterinary Science, Pennsylvania State University, University Park 16802, USA.
Mastro
A M
AM
Eskew
M L
ML
Hildenbrandt
G
G
Reddy
P V
PV
Reddy
C C
CC
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001692:Biological Transport; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020404:Glycerophospholipids; D008213:Lymphocyte Activation; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013110:Sphingosine / Q000008:administration & dosage*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage*
D004791:Enzyme Inhibitors; D020404:Glycerophospholipids; D010712:Phosphatidic Acids; C051521:phosphatidylethanol; D016718:Arachidonic Acid; D011493:Protein Kinase C; D010739:Phospholipase D; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate