HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, W. Articles by Kulmacz, R. J. Search for Related Content PubMed PubMed Citation Articles by Liu, W. Articles by Kulmacz, R. J.

Divergent cyclooxygenase responses to fatty acid structure and peroxide level in fish and mammalian prostaglandin H synthases

Wen Liu^*, Dazhe Cao^*,1, Sungwhan F. Oh, Charles N. Serhan and Richard J. Kulmacz^*,2

^* Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA; and

Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

¹Correspondence: Department of Internal Medicine, University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX 77030, USA. E-mail: richard.j.kulmacz{at}uth.tmc.edu

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 docosahexaenoate (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.

Key Words: cyclooxygenase substrate specificity • cyclooxygenase activation by peroxide • aspirin-induced lipoxygenase catalysis

This article has been cited by other articles:

				M. Wada, C. J. DeLong, Y. H. Hong, C. J. Rieke, I. Song, R. S. Sidhu, C. Yuan, M. Warnock, A. H. Schmaier, C. Yokoyama, et al. Enzymes and Receptors of Prostaglandin Pathways with Arachidonic Acid-derived Versus Eicosapentaenoic Acid-derived Substrates and Products J. Biol. Chem., August 3, 2007; 282(31): 22254 - 22266. [Abstract] [Full Text] [PDF]