The phospholipase A1 activity of lysophospholipase A-I links platelet activation to LPA production during blood coagulation.
J Lipid Res
; 52(5): 958-70, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21393252
ABSTRACT
Platelet activation initiates an upsurge in polyunsaturated (182 and 204) lysophosphatidic acid (LPA) production. The biochemical pathway(s) responsible for LPA production during blood clotting are not yet fully understood. Here we describe the purification of a phospholipase A(1) (PLA(1)) from thrombin-activated human platelets using sequential chromatographic steps followed by fluorophosphonate (FP)-biotin affinity labeling and proteomics characterization that identified acyl-protein thioesterase 1 (APT1), also known as lysophospholipase A-I (LYPLA-I; accession code O75608) as a novel PLA(1). Addition of this recombinant PLA(1) significantly increased the production of sn-2-esterified polyunsaturated LPCs and the corresponding LPAs in plasma. We examined the regioisomeric preference of lysophospholipase D/autotaxin (ATX), which is the subsequent step in LPA production. To prevent acyl migration, ether-linked regioisomers of oleyl-sn-glycero-3-phosphocholine (lyso-PAF) were synthesized. ATX preferred the sn-1 to the sn-2 regioisomer of lyso-PAF. We propose the following LPA production pathway in blood 1) Activated platelets release PLA(1); 2) PLA(1) generates a pool of sn-2 lysophospholipids; 3) These newly generated sn-2 lysophospholipids undergo acyl migration to yield sn-1 lysophospholipids, which are the preferred substrates of ATX; and 4) ATX cleaves the sn-1 lysophospholipids to generate sn-1 LPA species containing predominantly 182 and 204 fatty acids.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Coagulação Sanguínea
/
Lisofosfolipídeos
/
Ativação Plaquetária
/
Fosfolipases A1
/
Lisofosfolipase
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2011
Tipo de documento:
Article