PMID- 19230851
OWN - NLM
STAT- MEDLINE
DCOM- 20091125
LR  - 20211020
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1791
IP  - 10
DP  - 2009 Oct
TI  - TLR-4 mediated group IVA phospholipase A(2) activation is phosphatidic acid 
      phosphohydrolase 1 and protein kinase C dependent.
PG  - 975-82
LID - 10.1016/j.bbalip.2009.02.002 [doi]
AB  - Group IVA phospholipase A(2) (GIVA PLA(2)) catalyzes the release of arachidonic 
      acid (AA) from the sn-2 position of glycerophospholipids. AA is then further 
      metabolized into terminal signaling molecules including numerous prostaglandins. 
      We have now demonstrated the involvement of phosphatidic acid phosphohydrolase 1 
      (PAP-1) and protein kinase C (PKC) in the Toll-like receptor-4 (TLR-4) activation 
      of GIVA PLA(2). We also studied the effect of PAP-1 and PKC on Ca+2 induced and 
      synergy enhanced GIVA PLA(2) activation. We observed that the AA release induced 
      by exposure of RAW 264.7 macrophages to the TLR-4 specific agonist Kdo(2)-Lipid A 
      is blocked by the PAP-1 inhibitors bromoenol lactone (BEL) and propranolol as 
      well as the PKC inhibitor Ro 31-8220; however these inhibitors did not reduce AA 
      release stimulated by Ca+2 influx induced by the P2X7 purinergic receptor agonist 
      ATP. Additionally, stimulation of cells with diacylglycerol (DAG), the product of 
      PAP-1 mediated hydrolysis, initiated AA release from unstimulated cells as well 
      as restored normal AA release from cells treated with PAP-1 inhibitors. Finally, 
      neither PAP-1 nor PKC inhibition reduced GIVA PLA(2) synergistic activation by 
      stimulation with Kdo(2)-Lipid A and ATP.
FAU - Grkovich, Andrej
AU  - Grkovich A
AD  - Department of Chemistry and Biochemistry, University of California, San Diego, La 
      Jolla, California 92093-0601, USA.
FAU - Armando, Aaron
AU  - Armando A
FAU - Quehenberger, Oswald
AU  - Quehenberger O
FAU - Dennis, Edward A
AU  - Dennis EA
LA  - eng
GR  - GM069338/GM/NIGMS NIH HHS/United States
GR  - U54 GM069338/GM/NIGMS NIH HHS/United States
GR  - R01 GM064611-06/GM/NIGMS NIH HHS/United States
GR  - R01 GM064611/GM/NIGMS NIH HHS/United States
GR  - GM64611/GM/NIGMS NIH HHS/United States
GR  - U54 GM069338-06/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090220
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Diglycerides)
RN  - 0 (Kdo2-lipid A)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Naphthalenes)
RN  - 0 (Pancreatitis-Associated Proteins)
RN  - 0 (Pla2g4a protein, mouse)
RN  - 0 (Pyrones)
RN  - 0 (REG3A protein, human)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 88070-98-8 (6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9G34HU7RV0 (Edetic Acid)
RN  - 9Y8NXQ24VQ (Propranolol)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.1.1.4 (Group IV Phospholipases A2)
RN  - EC 3.1.3.4 (Phosphatidate Phosphatase)
SB  - IM
MH  - Adenosine Triphosphate/pharmacology
MH  - Animals
MH  - Arachidonic Acid/metabolism
MH  - Diglycerides/pharmacology
MH  - Drug Synergism
MH  - Edetic Acid/pharmacology
MH  - Egtazic Acid/pharmacology
MH  - Enzyme Activation/drug effects
MH  - Group IV Phospholipases A2/antagonists & inhibitors/*metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/drug effects/enzymology/metabolism
MH  - Mice
MH  - Naphthalenes/pharmacology
MH  - Pancreatitis-Associated Proteins
MH  - Phosphatidate Phosphatase/*metabolism
MH  - Propranolol/pharmacology
MH  - Protein Kinase C/antagonists & inhibitors/*metabolism
MH  - Pyrones/pharmacology
MH  - Time Factors
MH  - Toll-Like Receptor 4/*metabolism
PMC - PMC2743746
MID - NIHMS97004
EDAT- 2009/02/24 09:00
MHDA- 2009/12/16 06:00
PMCR- 2010/10/01
CRDT- 2009/02/24 09:00
PHST- 2008/09/12 00:00 [received]
PHST- 2009/02/04 00:00 [revised]
PHST- 2009/02/06 00:00 [accepted]
PHST- 2009/02/24 09:00 [entrez]
PHST- 2009/02/24 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - S1388-1981(09)00045-6 [pii]
AID - 10.1016/j.bbalip.2009.02.002 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2009 Oct;1791(10):975-82. doi: 
      10.1016/j.bbalip.2009.02.002. Epub 2009 Feb 20.