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Divergent cyclooxygenase responses to fatty acid structure and peroxide level in fish and mammalian prostaglandin H synthases
Author(s) -
Liu Wen,
Cao Dazhe,
Oh Sungwhan F.,
Serhan Charles N.,
Kulmacz Richard J.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-5273com
Subject(s) - trout , prostanoid , biochemistry , cyclooxygenase , rainbow trout , biology , activator (genetics) , enzyme , prostaglandin , chemistry , microbiology and biotechnology , receptor , fish <actinopterygii> , fishery
Prostanoid synthesis in mammalian tissues is regulated at the level of prostaglandin H synthase (PGHS) cyclooxygenase catalysis by the availability and structure of substrate fatty acid and the availability of peroxide activator. Two major PGHS isoforms, with distinct pathophysiological functions and catalytic regulation, have been characterized in mammals; a functionally homologous PGHS isoform pair has been cloned from an evolutionarily distant vertebrate, brook trout. The cyclooxygenase activities of recombinant brook trout PGHS‐1 and ‐2 were characterized to test the generality of mammalian regulatory paradigms for substrate specificity, peroxide activation, and product shifting by aspirin. Both trout cyclooxygenases had much more restrictive substrate specificities than their mammalian counterparts, with pronounced discrimination toward arachidonate (20: 4n‐6) and against eicosapentaenoate (20:5n‐3) and do‐cosahexaenoate (22:6n‐3), the latter two prominent in trout tissue lipids. Aspirin treatment did not increase lipoxygenase‐type catalysis by either trout enzyme. Both trout enzymes had higher requirements for peroxide activator than their mammalian counterparts, though the preferential peroxide activation of PGHS‐2 over PGHS‐1 seen in mammals was conserved in the fish enzymes. The divergence in cyclooxygenase characteristics between the trout and mammalian PGHS proteins may reflect accomodations to differences among vertebrates in tissue lipid composition and general redox state.—Liu, W., Cao, D., Oh, S. F., Serhan, C. N., Kulmacz, R. J. Divergent cyclooxygenase responses to fatty acid structure and peroxide level in fish and mammalian prostaglandin H synthases. FASEB J. 20, 1097–1108 (2006)