Two inducible, functional cyclooxygenase-2 genes are present in the rainbow trout genome.
The cyclooxygenases (Cox) catalyze the initial reactions in prostanoid biosynthesis, and produce the common prostanoids precursor, PGH(2). Mammalian species have two Cox isoforms; constitutively expressed cyclooxygenase-1 (Cox-1) and inducible cyclooxygenase-2 (Cox-2). Database searches suggest three Cox genes are present in many fish species. In this study, we cloned and characterized a second Cox-2 cDNA, Cox-2b, from the rainbow trout. Rainbow trout Cox-2b protein contains all the functionally important conserved amino acids for Cox enzyme activity. Moreover, the Cox-2b message contains AU-rich elements (AREs) in the 3' untranslated region (3'UTR) characteristic of inducible Cox-2 mRNAs. We took advantage of the existence of a rainbow trout cell line to demonstrate that expression from both the originally reported Cox-2 (Cox-2a) and Cox-2b genes is inducible. However, differential induction responses to alternative inducers are observed for rainbow trout Cox-2a and Cox-2b. Both Cox-2a and Cox-2b proteins expressed in COS cells are enzymatically active. Thus the rainbow trout has two functional, inducible Cox-2 genes. The zebrafish also contains two Cox-2 genes. However, genome structure analysis suggests diversion of the Cox-2a gene between zebrafish and rainbow trout.
Ishikawa
Tomo-o
TO
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA.
Herschman
Harvey R
HR
D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D017124:Conserved Sequence; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004790:Enzyme Induction; D005091:Exons; D014644:Genetic Variation; D016678:Genome; D007438:Introns; D007527:Isoenzymes / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D017686:Oncorhynchus mykiss / Q000235:genetics*; D016366:Open Reading Frames; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D020413:3' Untranslated Regions; D018076:DNA, Complementary; D007527:Isoenzymes; D012333:RNA, Messenger; D051546:Cyclooxygenase 2