Regulation of agonist-induced prostaglandin E1 versus prostaglandin E2 production: A mass analysis

Daniel Rubin, Michael Laposata

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2), derived by enzymatic oxidation of cellular dihomogammalinolenic acid (DHLA) and arachidonic acid (AA), respectively, have diverse and, at times, distinct biological actions. It has been suggested that PGE1 specifically inhibits a variety of inflammatory processes, and, in light of the potential therapeutic benefit of PGE1 and its fatty acid precursor in inflammatory disorders, there is growing interest in the biochemical mechanisms which determine the balance between PGE1 and PGE2 synthesis. Metabolic studies in this area have been hampered by the difficulties in measuring the extremely small masses of these prostaglandins which are generated in cell culture systems. We studied the regulation of PGE1 versus PGE2 synthesis using an essential fatty acid-deficient, PGE-producing, mouse fibrosarcoma cell line, EFD-1. Because EFD-1 cells contain no endogenous AA or DHLA, we were able to replete the cells with AA and DHLA of known specific activities; thus, the mass of both cellular AA and DHLA, and synthesized PGE1 and PGE2, could be accurately determined. The major finding of this study is that production of PGE2 was highly favored over production of PGE1 due to preferential incorporation of AA versus DHLA into, and release from, the total cellular phospholipid pool. Further, we correlated the selective release of AA versus DHLA from total cellular phospholipids with the selective incorporation of AA versus DHLA into specific phospholipid pools. In addition, we showed that conversion of DHLA to AA by Δ5 desaturase was enhanced by increasing the cellular mass of n - 6 fatty acids and by increasing the cell proliferative activity. Together, these results indicate that the relative abundance of PGE2 versus PGE1 in vivo is not merely a function of the relative abundance of AA versus DHLA in tissues, but also relates to markedly different cellular metabolism of these two fatty acids.

Original languageEnglish (US)
Pages (from-to)23618-23623
Number of pages6
JournalJournal of Biological Chemistry
Volume266
Issue number35
StatePublished - Dec 15 1991
Externally publishedYes

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8,11,14-Eicosatrienoic Acid
Alprostadil
Dinoprostone
Arachidonic Acid
Phospholipids
Fatty Acids
Essential Fatty Acids
Fibrosarcoma
Prostaglandins E
Cell culture
Metabolism
Prostaglandins
Cell Culture Techniques
Cells
Tissue

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of agonist-induced prostaglandin E1 versus prostaglandin E2 production : A mass analysis. / Rubin, Daniel; Laposata, Michael.

In: Journal of Biological Chemistry, Vol. 266, No. 35, 15.12.1991, p. 23618-23623.

Research output: Contribution to journalArticle

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