Role of sphingolipids in arachidonic acid metabolism.
J Pharmacol Sci
; 124(3): 307-12, 2014.
Article
em En
| MEDLINE
| ID: mdl-24599139
ABSTRACT
The arachidonic acid (AA) cascade is regulated mainly by the actions of two rate-limiting enzymes, phospholipase A2 (PLA2) and inducible cyclooxygenase-2 (COX-2). PLA2 acts to generate AA, which serves as the precursor substrate for COX-2 in the metabolic pathway leading to prostaglandin production. Amongst more than 30 members of the PLA2 family, cytosolic PLA2α (cPLA2α, group IVA) plays a major role in releasing AA from cellular membranes. Sphingolipids are a novel class of bioactive lipids that play key roles in the regulation of several cellular processes including growth, differentiation, inflammatory responses, and apoptosis. Recent studies implicated a regulatory function of sphingolipids in prostaglandin production. Whereas ceramide-1-phosphate and lactosylceramide activate cPLA2α directly, sphingosine-1-phosphate induces COX-2 expression. Sphingomyelin has been shown to inhibit the activity of cPLA2α. In addition, several sphingolipid analogs including a therapeutic agent currently used clinically are also reported to be inhibitors of cPLA2α. This review explores the role of sphingolipids in the regulation of cPLA2α and COX-2.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esfingolipídeos
/
Ácido Araquidônico
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Pharmacol Sci
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Japão