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Role of sphingolipids in arachidonic acid metabolism.
J Pharmacol Sci 2014; 124(3):307-12JP

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.

Authors+Show Affiliations

Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Japan.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

24599139

Citation

Nakamura, Hiroyuki, and Toshihiko Murayama. "Role of Sphingolipids in Arachidonic Acid Metabolism." Journal of Pharmacological Sciences, vol. 124, no. 3, 2014, pp. 307-12.
Nakamura H, Murayama T. Role of sphingolipids in arachidonic acid metabolism. J Pharmacol Sci. 2014;124(3):307-12.
Nakamura, H., & Murayama, T. (2014). Role of sphingolipids in arachidonic acid metabolism. Journal of Pharmacological Sciences, 124(3), pp. 307-12.
Nakamura H, Murayama T. Role of Sphingolipids in Arachidonic Acid Metabolism. J Pharmacol Sci. 2014;124(3):307-12. PubMed PMID: 24599139.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of sphingolipids in arachidonic acid metabolism. AU - Nakamura,Hiroyuki, AU - Murayama,Toshihiko, Y1 - 2014/03/04/ PY - 2014/3/7/entrez PY - 2014/3/7/pubmed PY - 2014/10/1/medline SP - 307 EP - 12 JF - Journal of pharmacological sciences JO - J. Pharmacol. Sci. VL - 124 IS - 3 N2 - 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. SN - 1347-8648 UR - https://www.unboundmedicine.com/medline/citation/24599139/Role_of_sphingolipids_in_arachidonic_acid_metabolism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/DN/JST.JSTAGE/jphs/13R18CP DB - PRIME DP - Unbound Medicine ER -