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Fluoride activates diradylglycerol and Superoxide generation in human neutrophils via PLD/PA phosphohydrolase‐dependent and ‐independent pathways
Author(s) -
Olson Susan C.,
Tyagi Shiv Raj,
Lambeth J.David
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80439-p
Subject(s) - chemistry , phosphatidic acid , phosphatidylethanol , superoxide , phospholipase d , diacylglycerol kinase , diglyceride , phospholipase c , fluoride , phospholipase , biochemistry , protein kinase c , receptor , phospholipid , enzyme , inorganic chemistry , membrane
In contrast to the rapid, ethanol‐inhibited Superoxide generation by the receptor‐linked agonist formyl‐methionyl‐leucyl‐phenylalanine (fMLP), fluoride‐activated Superoxide generation occurs after a prolonged lag, and as shown herein is relatively ethanol‐insensitive. We have investigated fluoride‐activation of diradylglycerol generation and phospholipase D activity. Fluoride induces a very large increase in diradylglycerol mass (both 1,2‐diacylglycerol (DAG) and 1‐ O ‐alkyl,2‐acylglycerol (EAG)), with kinetics similar to Superoxide generation. Unlike fMLP‐activated diglyceride generation which is completely inhibited by ethanol, that produced by fluoride is only partially (30%) blocked. When the phosphatidylcholine pool is 3 H‐prelabeled, fluoride activates both [ 3 H]phosphatidic acid (PA) and [ 3 H]diglyceride generation with similar kinetics. Partial inhibition of the production of these species by ethanol was seen, coincident with the appearance of [ 3 H]phosphatidylethanol, indicating phospholipase D‐dependent transphosphatidylation had occurred. The data are consistent with the fluoride activation of PA and diglyceride generation by both phospholipase D‐dependent and ‐independent (presumably phospholipase C) mechanisms.