Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages
Lysophosphatidylcholine (lysoPC) is a bioactive phospholipid that is involved in atherogenesis and inflammatory processes. However, the present understanding of mechanisms whereby lysophosphatidylcholine exerts its pathophysiological actions is incomplete. In the present work, we show that lysoPC st...
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doaj-6740bae2d24549f2bc8a418ab2bdda1c2021-04-27T04:45:18ZengElsevierJournal of Lipid Research0022-22751999-06-01406988993Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophagesAntonio Gómez-Muñoz0Lori O'Brien1Rajinder Hundal2Urs P. Steinbrecher3Division of Gastroenterology, Department of Medicine, The University of British Columbia, Vancouver, B.C., Canada V5Z 4E3Division of Gastroenterology, Department of Medicine, The University of British Columbia, Vancouver, B.C., Canada V5Z 4E3Division of Gastroenterology, Department of Medicine, The University of British Columbia, Vancouver, B.C., Canada V5Z 4E3To whom correspondence should be addressed.; Division of Gastroenterology, Department of Medicine, The University of British Columbia, Vancouver, B.C., Canada V5Z 4E3Lysophosphatidylcholine (lysoPC) is a bioactive phospholipid that is involved in atherogenesis and inflammatory processes. However, the present understanding of mechanisms whereby lysophosphatidylcholine exerts its pathophysiological actions is incomplete. In the present work, we show that lysoPC stimulates phospholipase D (PLD) activity in mouse peritoneal macrophages. PLD activation leads to the generation of important second messengers such as phosphatidic acid, lysophosphatidic acid, and diacylglycerol, all of which can regulate cellular responses involved in atherogenesis and inflammation. The activation of PLD by lysoPC was attenuated by down-regulation of protein kinase C activity with prolonged incubation with 100 nm of 4β-phorbol 12-myristate 13-acetate (PMA). Preincubation of the macrophages with the tyrosine kinase inhibitor genistein also decreased the stimulation of PLD by lysoPC, while pretreatment with orthovanadate, which inhibits tyrosine phosphatases, enhanced basal and lysoPC-stimulated PLD activity. The activation of PLD by lysoPC was attenuated by the platelet activating factor (PAF) receptor antagonist WEB-2086, suggesting a role for PAF receptor activation in this process. Furthermore, acetylation of lysoPC substantially increased its potency in activating PLD, suggesting that a cellular metabolite of lysoPC such as 1-acyl 2-acetyl PC might be responsible for at least part of the effect of lysoPC on PLD.—Gómez-Muñoz, A., L. O'Brien, R. Hundal, and U. P. Steinbrecher. Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages. J. Lipid Res. 1999. 40: 988–993.http://www.sciencedirect.com/science/article/pii/S0022227520335021lysophosphatidylcholinephospholipase Dprotein kinase Cmacrophages |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Antonio Gómez-Muñoz Lori O'Brien Rajinder Hundal Urs P. Steinbrecher |
spellingShingle |
Antonio Gómez-Muñoz Lori O'Brien Rajinder Hundal Urs P. Steinbrecher Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages Journal of Lipid Research lysophosphatidylcholine phospholipase D protein kinase C macrophages |
author_facet |
Antonio Gómez-Muñoz Lori O'Brien Rajinder Hundal Urs P. Steinbrecher |
author_sort |
Antonio Gómez-Muñoz |
title |
Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages |
title_short |
Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages |
title_full |
Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages |
title_fullStr |
Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages |
title_full_unstemmed |
Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages |
title_sort |
lysophosphatidylcholine stimulates phospholipase d activity in mouse peritoneal macrophages |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
1999-06-01 |
description |
Lysophosphatidylcholine (lysoPC) is a bioactive phospholipid that is involved in atherogenesis and inflammatory processes. However, the present understanding of mechanisms whereby lysophosphatidylcholine exerts its pathophysiological actions is incomplete. In the present work, we show that lysoPC stimulates phospholipase D (PLD) activity in mouse peritoneal macrophages. PLD activation leads to the generation of important second messengers such as phosphatidic acid, lysophosphatidic acid, and diacylglycerol, all of which can regulate cellular responses involved in atherogenesis and inflammation. The activation of PLD by lysoPC was attenuated by down-regulation of protein kinase C activity with prolonged incubation with 100 nm of 4β-phorbol 12-myristate 13-acetate (PMA). Preincubation of the macrophages with the tyrosine kinase inhibitor genistein also decreased the stimulation of PLD by lysoPC, while pretreatment with orthovanadate, which inhibits tyrosine phosphatases, enhanced basal and lysoPC-stimulated PLD activity. The activation of PLD by lysoPC was attenuated by the platelet activating factor (PAF) receptor antagonist WEB-2086, suggesting a role for PAF receptor activation in this process. Furthermore, acetylation of lysoPC substantially increased its potency in activating PLD, suggesting that a cellular metabolite of lysoPC such as 1-acyl 2-acetyl PC might be responsible for at least part of the effect of lysoPC on PLD.—Gómez-Muñoz, A., L. O'Brien, R. Hundal, and U. P. Steinbrecher. Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages. J. Lipid Res. 1999. 40: 988–993. |
topic |
lysophosphatidylcholine phospholipase D protein kinase C macrophages |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520335021 |
work_keys_str_mv |
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