PMID- 20061396
OWN - NLM
STAT- MEDLINE
DCOM- 20100429
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 285
IP  - 10
DP  - 2010 Mar 5
TI  - Phospholipid-esterified eicosanoids are generated in agonist-activated human 
      platelets and enhance tissue factor-dependent thrombin generation.
PG  - 6891-903
LID - 10.1074/jbc.M109.078428 [doi]
AB  - Here, a group of specific lipids, comprising phosphatidylethanolamine (PE)- or 
      phosphatidylcholine (PC)-esterified 12S-hydroxyeicosatetraenoic acid (12S-HETE), 
      generated by 12-lipoxygenase was identified and characterized. 12S-HETE-PE/PCs 
      were formed within 5 min of activation by thrombin, ionophore, or collagen. 
      Esterified HETE levels generated in response to thrombin were 5.85 +/- 1.42 (PE) 
      or 18.35 +/- 4.61 (PC), whereas free was 65.5 +/- 17.6 ng/4 x 10(7) cells (n = 5 
      separate donors, mean +/- S.E.). Their generation was stimulated by triggering 
      protease-activated receptors-1 and -4 and signaling via Ca(2+) mobilization 
      secretory phospholipase A2, platelet-activating factor-acetylhydrolase, src 
      tyrosine kinases, and protein kinase C. Stable isotope labeling showed that they 
      form predominantly by esterification that occurs on the same time scale as free 
      acid generation. Unlike free 12S-HETE that is secreted, esterified HETEs remain 
      cell-associated, with HETE-PEs migrating to the outside of the plasma membrane. 
      12-Lipoxygenase inhibition attenuated externalization of native PE and 
      phosphatidylserine and HETE-PEs. Platelets from a patient with the bleeding 
      disorder, Scott syndrome, did not externalize HETE-PEs, and liposomes 
      supplemented with HETE-PC dose-dependently enhanced tissue factor-dependent 
      thrombin generation in vitro. This suggests a role for these novel lipids in 
      promoting coagulation. Thus, oxidized phospholipids form by receptor/agonist 
      mechanisms, not merely as an undesirable consequence of vascular and inflammatory 
      disease.
FAU - Thomas, Christopher P
AU  - Thomas CP
AD  - Department of Infection, Cardiff University, Cardiff CF14 4XN, United Kingdom.
FAU - Morgan, Lloyd T
AU  - Morgan LT
FAU - Maskrey, Benjamin H
AU  - Maskrey BH
FAU - Murphy, Robert C
AU  - Murphy RC
FAU - Kuhn, Hartmut
AU  - Kuhn H
FAU - Hazen, Stanley L
AU  - Hazen SL
FAU - Goodall, Alison H
AU  - Goodall AH
FAU - Hamali, Hassan A
AU  - Hamali HA
FAU - Collins, Peter W
AU  - Collins PW
FAU - O'Donnell, Valerie B
AU  - O'Donnell VB
LA  - eng
GR  - U54 GM069338/GM/NIGMS NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - P01 HL087018-020001/HL/NHLBI NIH HHS/United States
GR  - GM069338/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100108
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Esters)
RN  - 0 (Phosphatidylcholines)
RN  - 0 (Phosphatidylethanolamines)
RN  - 59985-28-3 (12-Hydroxy-5,8,10,14-eicosatetraenoic Acid)
RN  - 9035-58-9 (Thromboplastin)
RN  - EC 1.13.11.31 (Arachidonate 12-Lipoxygenase)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - *12-Hydroxy-5,8,10,14-eicosatetraenoic Acid/chemistry/metabolism
MH  - Animals
MH  - Arachidonate 12-Lipoxygenase/metabolism
MH  - Blood Platelets/*metabolism
MH  - Esters/*chemistry/metabolism
MH  - Humans
MH  - Molecular Structure
MH  - Phosphatidylcholines/chemistry/*metabolism
MH  - Phosphatidylethanolamines/chemistry/*metabolism
MH  - Signal Transduction/physiology
MH  - Thrombin/*metabolism
MH  - Thromboplastin/*metabolism
PMC - PMC2844139
EDAT- 2010/01/12 06:00
MHDA- 2010/04/30 06:00
PMCR- 2010/01/08
CRDT- 2010/01/12 06:00
PHST- 2010/01/12 06:00 [entrez]
PHST- 2010/01/12 06:00 [pubmed]
PHST- 2010/04/30 06:00 [medline]
PHST- 2010/01/08 00:00 [pmc-release]
AID - S0021-9258(19)58678-1 [pii]
AID - M109.078428 [pii]
AID - 10.1074/jbc.M109.078428 [doi]
PST - ppublish
SO  - J Biol Chem. 2010 Mar 5;285(10):6891-903. doi: 10.1074/jbc.M109.078428. Epub 2010 
      Jan 8.