ReviewCytochrome P450 (CYP) in fish
Highlights
āŗ We present an overview of the CYP families in fish. āŗ We reviewed CYP genes in fish. āŗ We reviewed characterization of fish CYPs. āŗ Cytochrome P450 (CYP) enzymes are members of the hemoprotein superfamily.
Introduction
The CYP gene superfamily consists of a large number of genes encoding P450 enzymes, which typically catalyze mono-oxygenase reactions involving molecular oxygen and an equivalent number of electrons. The enzymes are involved in the detoxification of exogenous chemicals such as drugs, chemical carcinogens, and environmental pollutants, and in the metabolism of endogenous substrates, such as steroids, fatty acids, vitamins, and prostanoids (Nebert et al., 2004).
Large amounts of pollutants, including pharmaceuticals used in human and veterinary medicine, are released into the environment from human activities. These pollutants are eventually dispersed in the aquatic environment through various routes, such as atmospheric deposition, direct discharge, land run-off, and food-chain transfer. Numerous studies of the CYP1A isoform in fish have demonstrated its utility as a biomarker for aquatic pollution (Fent, 2003, Moore et al., 2003, Williams et al., 1998). For example, CYP1A1-dependent ethoxyresorufin O-deethylase (EROD) activity is used as an indicator of environmental contamination by polycyclic aromatic hydrocarbons and dioxins (Orrego et al., 2005, Parente et al., 2008, Schlezinger and Stegeman, 2001). Thus, the study of fish P450 contributes to the monitoring of environmental chemicals, as well as increasing our understanding of marine biology.
In the late 1980s, the presence of CYP was shown in the livers of rainbow trout and other fishes (Heilmann et al., 1988, Melancon et al., 1981, Stegeman, 1989, Winkelhake et al., 1983, Winston et al., 1988). Multiple forms of CYPs have been detected, predominantly in the liver. CYP genes have been cloned, and characterized from numerous freshwater and marine fish. Analysis of the Japanese pufferfish (or Fugu) genome has revealed 54 CYP genes (Nelson, 2003). Currently, 18 CYP gene families, CYP1, CYP2, CYP3, CYP4, CYP5, CYP7, CYP8, CYP11, CYP17, CYP19, CYP20, CYP21, CYP24, CYP26, CYP27, CYP39, CYP46 and CYP51 have been identified in fish (Table 1) [http://www.bioscience.org/guides/format.pdf] (Nelson, 2003).
In fish, the CYP1 family consists of four subfamilies, CYP1A, CYP1B, CYP1C and CYP1D. CYP1A gene products catalyze the oxidation of environmental carcinogens, and are therefore critical determinants in pathways leading either to detoxification and excretion or to DNA adduct formation and carcinogenesis (Gelboin, 1980). In fish, CYP1A subfamily plays important roles in the metabolism and activation of carcinogenesis and is used as a biomarker to assess contamination of the aquatic environment (Brammell et al., 2010, Goksoyr, 1995, Jung et al., 2011, Nilsen et al., 1998). cDNAs encoding CYP1A enzymes have been isolated from various fish species such as rainbow trout (Oncorhynchys mykiss) (Rabergh et al., 2000), mummichog (Fundulus heteroclitus) (Morrison et al., 1998), European sea bass (Dicentrarchus labrax) (Stien et al., 1998), Atlantic salmon (Salmo salar) (Arukwe, 2002), medaka (Oryzias latipes) (Kim et al., 2004), yellow catfish (Pelteobagrus fulvidraco) (Kim et al., 2008a), crucian carp (hybridized Prussian carp) (Fu et al., 2011) and hermaphroditic fish, mangrove killifish (Rivulus marmoratus) (Lee et al., 2005). The fish CYP1A subfamily of enzymes metabolizes various substrates. Rainbow trout CYP1A catalyzes 7-ethoxyresorufin O-deethylation and ibuprofen 2OH-hydroxylation (Gomez et al., 2011, Levine and Oris, 1999). CYP1A from the liver of feral leaping mullet (Liza saliens) shows a high substrate specificity for 7-ethoxyresorufin and methoxyresorufin (Sen and Arinc, 2000). CYP1A is the major enzyme involved in catabolism of pregnenolone in the rainbow trout embryo (Petkam et al., 2003a, Petkam et al., 2003b). CYP1A expressed from zebrafish (Danio rerio) cDNA metabolizes 7-ethoxyresorufin, estradiol and benzopyrene (Chung et al., 2004, Scornaienchi et al., 2010a, Scornaienchi et al., 2010b). E. coli transformed with CYP1A9 cDNA from Japanese eel (Anguilla japonica) bioconverts estradiol and flavanone (Uno et al., 2008).
Four P450 type 1 family enzymes (CYP1B, CYP1C1, CYP1C2 and CYP1D) have been isolated from diverse fish species. CYP1B1 cDNAs have been isolated from two teleost fish species (scup, Stenotomus chrysops (Godard et al., 2000) and European plaice, Pleuronectes platessa (Godard et al., 2000)), as well as the common carp (Cyprinus carpio) (El-kady et al., 2004). CYP1C cDNAs have been isolated from scup (Godard et al., 2000), the common carp (Cyprinus carpio) (Itakura et al., 2005) and mummichog (F. heteroclitus) (Wang et al., 2006), and CYP1D cDNAs have been isolated from the three-spined stickleback (Gasterosteus aculeatus), killifish, medaka and zebrafish (Goldstone and Stegeman, 2008, Zanette et al., 2009).
Expression of CYP1D1 mRNA is not induced by aryl hydrocarbon receptor agonist (Goldstone et al., 2010, Zanette et al., 2009). CYP1B1, CYP1C1 and CYP1C2 expressed from zebrafish (D. rerio) cDNA metabolizes resorufin based-substrate, estradiol and benzopyrene (Scornaienchi et al., 2010a, Scornaienchi et al., 2010b). Analysis of amino acid sequence domains suggests that fish CYP1B, CYP1C and CYP1D have unique catalytic functions or substrates; however, the function of these P450s is little known. Further, CYP1C has not been identified in mammals. Therefore, CYP1C may have fish-specific catalytic activities. Lately CYP1D1 gene was identified in monkey and CYP1D1 protein catalyzed ethoxyresorufin O-deethylation and caffeine 8-hydroxylation (Kawai et al., 2010, Uno et al., 2011). Fish CYP1D may metabolize these substrates.
Expression of fish CYP1 family mRNA, like that in mammals, is induced by various compounds such as polychlorinated biphenyls (PCB), beta-naphthoflavone, cobalt, zinc, benzopyrene, pesticides and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Bugiak and Weber, 2009, Calo et al., 2009, Ceyhun et al., 2011, Ceyhun et al., 2012, Chung-Davidson et al., 2004, Jonsson et al., 2007, Kim et al., 2008b, Rabergh et al., 2000, Sanden and Olsvik, 2009, Zanette et al., 2009). In mammals, the expression of the mRNA of CYP1 families is regulated by a cytosolic transcriptional factor, aryl hydrocarbon receptor (Ah receptor) (Beischlag et al., 2008, Gu et al., 2000). Ah receptor has a high affinity to planar compounds, such as dioxins and polyaromatic hydrocarbons (PAHs). In the nucleus, Ah receptor forms a complex with the Ah receptor nuclear translocator (Arnt), which subsequently binds to the xenobiotic response element (XRE, or dioxin response element DRE) in the 5ā²-upstream region of CYP1A and CYP1B genes. Ah receptor is a member of the basic helix-loop-helix Per-Arnt-Sim (bHLH-PAS) super family of proteins, and is widely distributed in vertebrates (Abel and Haarmann-Stemmann, 2010). An Ah receptor homolog is also found in fish. In mammals, Ah receptor is reported to be single gene. In contrast, two putative Ah receptor genes, designated as Ah receptor 1 and Ah receptor 2, have been identified in the mummichog (F. heteroclitus) (Hahn et al., 1997), zebrafish (Andreasen et al., 2002), medaka, and two species of pufferfish (Takifugu rubripes and Tetraodon fluviatilis) (Hahn, 2001). CYP1A mRNA expression is induced by miniscule amounts of diverse aromatic compounds, and thus it is used as a sensitive biomarker of exposure to organic contaminants. In comparison to the single Ah receptor in mammals, the two Ah receptors in fish may allow more complex regulation of CYP1A gene expression. Lately knockdown of the Ah receptor 2 protected against the cardiac toxicity of PAHs in killifish and zebrafish (Clark et al., 2010, Van Tiem and Di Giulio, 2011).
cDNAs encoding the CYP2 family of enzymes, CYP2K, CYP2M, CYP2N, CYP2P and CYP2X, have been isolated from diverse fish species. In Japanese pufferfish, the genes encoding members (enzymes) in CYP2K, CYP2N, CYP2P, CYP2R, CYP2U, CYP2X, CYP2Y and CYP2Z have been reported. Within the CYP superfamily, the CYP2 family shows the largest degree of divergence across species. Only two CYP2 subfamilies, CYP2R1 and CYP2U1, appear to be evolutionarily conserved (Nelson, 2003). In mammals, CYP2R1 and CYP2U1 metabolize the endogenous substrates vitamin D and arachidonic acid, respectively (Cheng et al., 2004, Chuang et al., 2004). cDNAs encoding CYP2K have been isolated from rainbow trout (Buhler et al., 1994) and zebrafish (Wang-Buhler et al., 2005). CYP2K1 has benzphetamine N-demethylase and steroid hydroxylase activities, and both CYP2K1 and CYP2K6 catalyze the oxidation of lauric acid at the (omega-1) position and the conversion of aflaotoxin B1 to its exo-8,9-epoxide (Yang et al., 2000). CYP2M1 isolated from rainbow trout liver shows lauric acid (omega-6)-hydroxylation activity (Yang et al., 1998). Exposure to produced formation water, the oily water usually discharged from a platform after the separation from the oil, induced CYP2K1 and CYP2M1 proteins in tropical fish (Zhu et al., 2008). Three genes encoding CYP2P have been cloned from a mummichog (F. heteroclitus), and CYP2P3 has been shown to catalyze benzphetamine N-demethylation and arachidonic acid oxidation (Oleksiak et al., 2003). CYP2N1 mRNA is abundant in liver and intestine, whereas CYP2N2 mRNA is abundant in heart and brain. Both CYP2N1 and CYP2N2 metabolize arachidonic acid to epoxyeicosatrienoic acid and have benzphetamine N-demethylation activity (Oleksiak et al., 2000). P4502X1 isolated from channel catfish (Ictalurus punctatus) catalyzes aminopyrine and benzphetamine demethylase activity (Mosadeghi et al., 2007, Schlenk et al., 2002).
In mammals, CYP2B genes are induced by phenobarbital (PB) and a large number of structurally diverse xenochemicals. In contrast, in fish, expression of CYP2 family mRNAs is not induced by PB-type inducers (Sadar et al., 1996). Furthermore, a PB-type inducer does not cause nuclear translocation of CAR, a nuclear receptor that can activate CYP2B genes in response to exogenous compounds in rodents (Iwata et al., 2002). Thus, in fish, the CYP2 family catalyzes foreign and endogenous compounds, but the gene regulatory systems may be different from those of mammals.
In fish, the CYP3 family consists of the CYP3A, CYP3B and CYP3C subfamilies (Yan and Cai, 2010). The CYP3A27 gene has been cloned from rainbow trout, and is distributed in the intestinal tract and the heart, in addition to the liver and genital gland (Lee et al., 2001). CYP3A45, whose sequence differs by 27 amino acids from that of CYP3A27, is expressed abundantly in the intestinal ceca of rainbow trout. CYP3A27 catalyzes testosterone and progesterone 6beta-hydroxylation, whereas CYP3A45 exhibits testosterone 6beta-hydroxylation activity (Lee and Buhler, 2003). The genes encoding CYP3A38 and CYP3A40 have been cloned from medaka. CYP3A38 shows testosterone 6beta- and 16beta-hydroxylase activity, whereas CYP3A40 catalyzes 2alpha- and 6beta-hydroxylation. CYP3A38 and CYP3A40 have been heterologously expressed in insect cells by means of baculovirus, and in a reconstitution system, the enzyme activity of CYP3A38 and CYP3A40 increases with increasing concentrations of benzyloxy-4-(trifluoromethyl)-coumarin and/or nonylphenol; however, the enzyme activity is suppressed at high concentrations of these compounds (Kashiwada et al., 2005). It was implied that they undergo allosteric changes (Kullman et al., 2004). Expression of CYP3A40 mRNA is not induced by synthetic polycyclic musks (Yamauchi et al., 2008). CYP3A30 and CYP3A56, which share 98% amino acid sequence identity, have been isolated from a mummichog, CYP3A30and CYP3A56 protein and mRNA are highly expressed in liver and intestine. Minor sites of expression, listed in descending order, are gill, spleen, kidney and brain. CYP3A protein expression is 2.5 fold higher in males than in females. In addition, killifish display sexual dimorphic expression of hepatic CYP3A proteins (Hegelund and Celander, 2003). CYP3A47, CYP3A48 and CYP3A49 have been shown, by analysis of the genome, to be expressed in Japanese pufferfish (Nelson, 2003). CYP3A65 cDNA has been cloned from zebrafish by RT-PCR. CYP3A65 protein expression is induced by treatment with dexamethasone, rifampicin, or TCDD. CYP3A65 mRNA expression is enhanced by TCDD treatment during early larval stages (Tseng et al., 2005). Exposure of p,pā-DDE and dieldrin alters CYP3A68 and CYP3A69 mRNA expression in largemouth bass (Micropterus salmoides) (Barber et al., 2007). CYP3A79 cDNA has been cloned from European sea bass using RACE-PCR. CYP3A79 mRNA expression is detected in liver, heart, and intestine, and this expression appears to be resistant to induction by such inducers as dexamethasone, 17beta-estradiol, prengnenolone 16alpha-carbonitrile, corticosterone, clotrimazole and dehydroepiandrosterone (DHEA) (Vaccaro et al., 2007). Lately CYP3A126 cDNA has been cloned from fathead minnow (Pimephales promelas) (Christen et al., 2010). CYP3B1 and CP3B2 mRNA are expressed in Japanese pufferfish, however, their identity as P450 enzymes has not been confirmed (Nelson, 2003).
The CYP3C1 gene, which is unique to fish, has been isolated by RT-PCR based on the nucleotide sequences of zebrafish CYP3A orthologs. CYP3C1 has 51%ā54% amino acid identity with CYP3A and CYP3B from other teleosts. CYP3C1 mRNA is expressed in the liver, intestine, and ovary in adult zebrafish. CYP3C1 mRNA is distributed through the whole zebrafish embryo, but its expression is specifically concentrated in brain at the larval stage. CYP3C1 has been expressed in yeast as a holoenzyme (Corley-Smith et al., 2006).
In mammals, expression of the CYP3A subfamily is induced by dexamethasone and rifampicin. Control of CYP3A expression is thought to be mediated by the Ah receptor/ARNT pathway in zebrafish, whereas, the pregnane X receptor (PXR) is suggested to activate CYP3A expression in Atlantic salmon (Finn, 2007).
Hydroxylation of fatty acids is catalyzed by the CYP4A and CYP4F subfamilies in mammals (Simpson, 1997). CYP4T1 cDNA has been cloned by RT-PCR using degenerate primers based on homologous regions in rainbow trout CYP4 proteins, and a 390-bp sequence encoding a 130 amino acid peptide has been obtained. The peptide shows amino acid identity to rat CYP4B2 (55.4%) and rabbit CYP4B1 (54.6%) (Falckh et al., 1997). CYP4T2 cDNA has been cloned by RT-PCR from European sea bass (D. labrax) treated with di(2-ethylhexyl) phthalate (DEHP). CYP4T2 shares 69 amino-acid identity with CYP4T1. CYP4T2 mRNA is abundant in kidney, and intraperitoneal injection of DEHP and 2,4-dichlorophenoxy acetic acid (2,4-D) induces CYP4T1 mRNA in kidney, but not in liver (Sabourault et al., 1998). The genes encoding CYP4T5 and CYP4F28 have been identified in the Japanese pufferfish genome; however, the enzymes are yet to be characterized (http://drnelson.utmem.edu/cytochromep450.html). CYP4T11 has been cloned from rare minnow (Gobiocypris rarus) and is expressed in liver and intestine with lower expression in the gill and brain (Liu et al., 2009). Clofibrate, which is a peroxisome proliferating agent and typical inducer of the CYP4A subfamily in mammals, induces hydroxylation of omega-, omega-4, and omega-5 lauric acid in the liver of the male bluegill, Lepomis macrochirus. Ciprofibrate also induces lauric acid hydroxylation in the male catfish kidney (Haasch et al., 1998). In contrast, laurate hydroxylase activity is not increased in the liver and extrahepatic tissues of rainbow trout following intraperitoneal injections of DEHP and DBP, or following waterborne exposure to DEHP and DBP (Cravedi and Perdu-Durand, 2002). Therefore, there may be species differences in the mode of induction of the CYP4 family in fish. Or, the catalytic activities/characteristics of CYP family enzymes may not be same among bluegill, catfish and rainbow trout.
Peroxisome proliferator-activated receptor alpha (PPARalpha), which is the transcriptional factor of the CYP4 family in mammals, has been shown by the use of anti-PPAR antibodies to be distributed primarily in the liver and intestinal tract in zebra fish (Ibabe et al., 2002).
CYP11A (or P450scc, P450 side-chain cleavage enzyme), localizes to the mitochondrial inner membrane, where it catalyses the rate-limiting initial step in steroid biosynthesis (i.e., the conversion of cholesterol to pregnenolone). CYP11B (or P45011beta) also localizes to the mitochondrial membrane, but is involved in the conversion of progesterone to cortisol in the adrenal cortex. The CYP11A gene has been identified in rainbow trout (Oncorhynchus mykiss) (Takahashi et al., 1993), southern stingray (Dasyatis americana) (Nunez and Trant, 1997), channel catfish (Genbank accession number AF063836), Japanese eel (Kazeto et al., 2006), zebrafish (Hsu et al., 2002), freshwater stingray (Potamotrygon motoro) (Scott Nunez et al., 2006), Nile tilapia (Zhang et al., 2010) and Japanese pufferfish (Nelson, 2003). In mammals CYP11A is primarily expressed in the adrenal, gonad, placenta, and to a lesser extent in the brain, skin and intestine (Guo et al., 2003). CYP11A1 transcriptional activities are regulated by trans-regulators such as SF-1, DAX-1, TreP-132, LBP and GATA (Shih et al., 2011). The expression of zebrafish CYP11A mRNA in ovarian follicles decreases as the follicles grow (Ings and Van Der Kraak, 2006). In the brain of protandrous black porgy fish (Acanthopagrus schlegeli), the expression of CYP11A mRNA increases with developmental age (Tomy et al., 2007). The genes encoding CYP11B have been isolated from rainbow trout (Kusakabe et al., 2002, Liu et al., 2000), European sea bass (Socorro et al., 2007), Japanese eel (Jiang et al., 1996) and Japanese pufferfish (Nelson, 2003). CYP11B1 is present primarily in the zona fasciculate/reticularis of the human adrenal cortex, whereas CYP11B2 expression is limited to the zona glomerulosa (Ishimura and Fujita, 1997). During spermatogenesis, CYP11B mRNA in the testis of rainbow trout shows a seasonal pattern similar to that of plasma androgens (Kusakabe et al., 2002).
In fish, various steroids and xenochemicals alter CYP11 gene expression. Treatment with androgen and estrogen decreases the level of CYP11A and CYP11B mRNA in the testis of rainbow trout (Baron et al., 2005), whereas treatment with androgen up-regulates CYP11A1mRNA in the female gonads of the same species (Govoroun et al., 2001). The xeno-estrogen, EE2 (17alpha-ethinylestradiol) up-regulates the expression of CYP11A in the oocytes of Atlantic salmon (Vang et al., 2007). Treatment with 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene increases the level of CYP11A mRNA in the brain, kidney and liver of Atlantic salmon (Arukwe, 2008). Exposure to the xeno-estrogen, 4-tert-pentylphenol, inhibits the mRNA expression of CYP11B in the gonads of medaka fish (Yokota et al., 2005).
CYP17 (or P450c17) is a steroidogenic enzyme responsible for the sequential 17alpha-hydroxylase and C17,20-lyase reactions(Zuber et al., 1986). CYP17 cDNAs have been isolated from ovary or testis in rainbow trout (Sakai et al., 1992), channel catfish (Genbank accession number, AF063837), spiny dogfish shark (Squalus acanthias) (Filby et al., 2007), zebrafish (Wang and Ge, 2004) and fathead minnow (P. promelas) (Halm et al., 2003). In mammals, CYP17 is predominantly expressed in the adrenal gland, testicular Leydig cells and ovarian thecal cells. The transcription of CYP17 is increased in response to the tropic hormone adrenocorticotropin (ACTH) signaling (Sewer and Jagarlapudi, 2009). When CYP17 from spiny dogfish shark is artificially expressed in yeast, progesterone and pregnenolone are completely metabolized to their respective androgens (androstenedione and DHEA) (Trant, 1996).
Expression of CYP17A mRNA is developmentally regulated. CYP17A mRNA expression in the ovaries of rainbow trout and Japanese eel increases during the development and maturation of the follicles (Kazeto et al., 2006, Sakai et al., 1992). In contrast, CYP17A mRNA expression in fathead minnow decreases with development (Halm et al., 2003) and zebrafish show no significant temporal differences in expression among developmental stages (Wang and Ge, 2004). In rainbow trout testis, the seasonal levels of CYP17A mRNA change dramatically and are closely related to the change in serum steroid levels (Kusakabe et al., 2006). In the brain of protandrous black porgy fish, CYP17 mRNA expression increases with developmental age (Tomy et al., 2007). The synthetic estrogen, EE2alpha inhibits the mRNA expression of CYP17 in the testis of fathead minnow and rainbow trout (Baron et al., 2005), whereas in the testis of fathead minnow the anti-androgen flutamide up-regulates the genes encoding CYP17 (Filby et al., 2007).
CYP19, which is also known as P450arom or aromatase, catalyzes the formation of aromatic C18 estrogen from C19 androgen, and is thus the terminal steroidogenic enzyme in the biosynthesis pathway of estrogen (Simpson et al., 1994). The gene encoding CYP19 has been cloned and characterized in fish such as Nile tilapia (Oreochromis niloticus) (Chang et al., 1997), rainbow trout (Tanaka et al., 1992), carp (C. carpio) (Barney et al., 2008), blue gourami (Trichogaster trichopterus) (Ezagouri et al., 2008), channel catfish (Trant, 1994), zebrafish (Chiang et al., 2001) and rice field eel (Monopterus albus) (Yu et al., 2008). CYP19 mRNA is expressed primarily in the gonads, pituitary and brain (Callard et al., 1981, Callard et al., 1983, Callard and Tchoudakova, 1997, Goto-Kazeto et al., 2004, Melo and Ramsdell, 2001). In mammals the expression of aromatase plays an important roles in the regulation of the reproductive cycle in females (Stocco, 2012). The brains of adult teleost fish, goldfish (Carassius auratus) and toadfish (Opsanus tau), have about 1000 times the level of aromatase activity found in brain of adult mammals (Pasmanik and Callard, 1985). In fish, two CYP19 genes encode structurally and functionally different isoforms, commonly termed CYP19A1 (or CYP19a) and CYP19A2 (or CYP19b). In zebrafish, carp, yellowtail clownfish and catfish; CYP19A1 mRNA is primary expressed in the gonads and plays important roles in sex differentiation and oocyte growth, whereas CYP19A2 mRNA is primarily expressed in the brain (Barney et al., 2008, Kishida and Callard, 2001, Kobayashi et al., 2010, Rasheeda et al., 2010). The physiological significance of brain CYP19A2 is related to estrogen-dependent neurogenesis, which is continuous through adulthood in fish (Forlano et al., 2001, Pellegrini et al., 2007), as well as sex change and behavior (Marsh et al., 2006) and the regulation of the gonadal-pituitary-hypothalamic feedback loop (Melo and Ramsdell, 2001, Villeneuve et al., 2007).
CYP19 catalyzes the final step in the conversion of androgens to estrogens, and therefore plays a role in the temperature-dependent sex determination of pejerrey (Odontesthes bonariensis); CYP19A1 mRNA expression during the temperature-dependent sex determination and gonadal sex differentiation period increases at the feminizing temperature and is suppressed at the masculinizing temperature (Karube et al., 2007). Yellow perch (Perca flavescens) exhibits an estrogen-stimulated sexual size dimorphism in which females grow faster and larger than males. In this species, CYP19a1a mRNA is highly expressed in the liver in females and is undetectable in the liver in males, suggesting its involvement in sexually dimorphic growth (Lynn et al., 2008). Treatment with aromatase inhibitors causes sex reversal in Nile tilapia (Afonso et al., 2001), honeycomb grouper (Epinephelus merra) (Bhandari et al., 2004a, Bhandari et al., 2004b) and zebrafish (Fenske and Segner, 2004). Treatment with estrogen increases aromatase activity by increasing CYP19b mRNA levels in zebrafish (Cheshenko et al., 2007). The synthetic estrogen EE2 increases CYP19a and CYP19b mRNA levels, while the antifoulant, tributyltin (TBT) decreases CYP19b mRNA levels in Atlantic salmon (Lyssimachou et al., 2006). In rare minnow and Atlantic salmon, xenoestrogen 4-nonylphenol decreases CYP19a mRNA levels (Kortner et al., 2009, Wang et al., 2010).
CYP26 family enzymes metabolize retinoic acid (RA) into its hydroxylated polar derivatives (Fujii et al., 1997, White et al., 1996). All-trans RA is metabolized by CYP26 to form 4-oxo-RA, 4-OH-RA, 18-OH-RA and 5,6-epoxy-RA (Fujii et al., 1997). RA plays crucial roles in vertebrate embryonic development and is essential for the establishment of the anterior-posterior pattern in hindbrain (Hernandez et al., 2007). CYP26A is a major RA-degrading enzyme during gastrulation (Abu-Abed et al., 2001). Three CYP26 genes (CYP26A1, CYP26B1 and CYP26C1) have been isolated from zebrafish (Gu et al., 2005, White et al., 1996, Zhao et al., 2005); three CYP26 genes have also been identified in Japanese pufferfish (Nelson, 2003). RNA expression data from adult human tissues indicated that CYP26 enzymes are expressed in a tissue-specific manner (White et al., 2000, Xi and Yang, 2008). In the zebrafish, the three CYP26 mRNA show dynamic and non-overlapping distributions in the developing embryo. In this species, overexpression of CYP26A1 in embryos suppresses the expression of posterior genes (Kudoh et al., 2002), and the combined depletion of CYP26A1, CYP26B1 and CYP26C1 results in severe posteriorization of the hindbrain (Hernandez et al., 2007). CYP2B1 is required to control osteogenesis in axial skeletogenesis (Spoorendonk et al., 2008).
References (163)
Complementary DNA cloning, sequence analysis and differential organ expression of beta-naphthoflavone-inducible cytochrome P4501A in Atlantic salmon (Salmo salar)
Comp. Biochem. Physiol. C Toxicol. Pharmacol.
(2002)- et al.
Exposure to p,pā-DDE or dieldrin during the reproductive season alters hepatic CYP expression in largemouth bass (Micropterus salmoides)
Aquat. Toxicol.
(2007) - et al.
Distinct cytochrome P450 aromatase isoforms in the common carp (cyprinus carpio): sexual dimorphism and onset of ontogenic expression
Gen. Comp. Endocrinol.
(2008) - et al.
Hepatic and vascular mRNA expression in adult zebrafish (Danio rerio) following exposure to benzo-a-pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin
Aquat. Toxicol.
(2009) - et al.
Cloning and sequencing of the major rainbow trout constitutive cytochrome P450 (CYP2K1): identification of a new cytochrome P450 gene subfamily and its expression in mature rainbow trout liver and trunk kidney
Arch. Biochem. Biophys.
(1994) - et al.
Biochemical evidence for aromatization of androgen to estrogen in the pituitary
Gen. Comp. Endocrinol.
(1981) - et al.
Evolutionary and functional significance of two CYP19 genes differentially expressed in brain and ovary of goldfish
J. Steroid Biochem. Mol. Biol.
(1997) - et al.
CYP2U1, a novel human thymus- and brain-specific cytochrome P450, catalyzes omega- and (omega-1)-hydroxylation of fatty acids
J. Biol. Chem.
(2004) - et al.
cDNA-directed expression of a functional zebrafish CYP1A in yeast
Aquat. Toxicol.
(2004) - et al.
AHR2 mediates cardiac teratogenesis of polycyclic aromatic hydrocarbons and PCB-126 in Atlantic killifish (Fundulus heteroclitus)
Aquat. Toxicol.
(2010)
CYP3C1, the first member of a new cytochrome P450 subfamily found in zebrafish (Danio rerio)
Biochem. Biophys. Res. Commun.
The phthalate diesters DEHP and DBP do not induce lauric acid hydroxylase activity in rainbow trout
Mar. Environ. Res.
Expression of the two cytochrome P450 aromatase genes in the male and female blue gourami (Trichogaster trichopterus) during the reproductive cycle
Gen. Comp. Endocrinol.
CYP4T1--a cytochrome P450 expressed in rainbow trout (Oncorhynchus mykiss) liver
Biochem. Biophys. Res. Commun.
Aromatase modulation alters gonadal differentiation in developing zebrafish (Danio rerio)
Aquat. Toxicol.
Ecotoxicological problems associated with contaminated sites
Toxicol. Lett.
Gene expression profiles revealing the mechanisms of anti-androgen- and estrogen-induced feminization in fish
Aquat. Toxicol.
The physiology and toxicology of salmonid eggs and larvae in relation to water quality criteria
Aquat. Toxicol.
Effects of cytochrome P450 1A substrate (difloxacin) on enzyme gene expression and pharmacokinetics in crucian carp (hybridized Prussian carp)
Environ. Toxicol. Pharmacol.
Identification of cytochrome P450 1B-like sequences in two teleost fish species (scup Stenotomus chrysops and plaice, Pleuronectes platessa) and in a cetacean (striped dolphin, Stenella coeruleoalba)
Mar. Environ. Res.
Gene structure of the novel cytochrome P4501D1 genes in stickleback (Gasterosteus aculeatus) and medaka (Oryzias latipes)
Mar. Environ. Res.
Localization and expression of aromatase mRNA in adult zebrafish
Gen. Comp. Endocrinol.
Molecular cloning and expression of a novel CYP26 gene (cyp26d1) during zebrafish early development
Gene Expr. Patterns
Induction of lauric acid hydroxylase activity in catfish and bluegill by peroxisome proliferating agents
Comp. Biochem. Physiol. C Pharmacol. Toxicol. Endocrinol.
Cloning and gene expression of P450 17alpha-hydroxylase,17,20-lyase cDNA in the gonads and brain of the fathead minnow Pimephales promelas
Gen. Comp. Endocrinol.
Hepatic versus extrahepatic expression of CYP3A30 and CYP3A56 in adult killifish (Fundulus heteroclitus)
Aquat. Toxicol.
Expression of zebrafish cyp11a1 as a maternal transcript and in yolk syncytial layer
Gene Expr. Patterns
Species-specific responses of constitutively active receptor (CAR)-CYP2B coupling: lack of CYP2B inducer-responsive nuclear translocation of CAR in marine teleost, scup (Stenotomus chrysops)
Comp. Biochem. Physiol. C Toxicol. Pharmacol.
Basal and 3,3ā,4,4ā,5-pentachlorobiphenyl-induced expression of cytochrome P450 1A, 1B and 1C genes in zebrafish
Toxicol. Appl. Pharmacol.
Biomarker responses in pelagic and benthic fish over 1 year following the Hebei Spirit oil spill (Taean, Korea)
Mar. Pollut. Bull.
Functional characterization of medaka CYP3A38 and CYP3A40: kinetics and catalysis by expression in a recombinant baculovirus system
Comp. Biochem. Physiol. C Toxicol. Pharmacol.
Cloning and characterization of a cDNA encoding cholesterol side-chain cleavage cytochrome P450 (CYP11A1): tissue-distribution and changes in the transcript abundance in ovarian tissue of Japanese eel, Anguilla japonica, during artificially induced sexual development
J. Steroid Biochem. Mol. Biol.
Cloning of cytochrome P450 1A (CYP1A) genes from the hermaphrodite fish Rivulus marmoratus and the Japanese medaka Oryzias latipes
Mar. Environ. Res.
Molecular cloning and beta-naphthoflavone-induced expression of a cytochrome P450 1A (CYP1A) gene from an anadromous river pufferfish, Takifugu obscurus
Mar. Pollut. Bull.
Sex- and tissue-specific expression of P450 aromatase (cyp19a1a) in the yellowtail clownfish, Amphiprion clarkii
Comp. Biochem. Physiol. A Mol. Integr. Physiol.
Neural aromatase transcript and protein levels in Atlantic salmon (Salmo salar) are modulated by the ubiquitous water pollutant, 4-nonylphenol
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Mar. Environ. Res.
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Arch. Biochem. Biophys.
Immunohistochemical localization and differential expression of cytochrome P450 3A27 in the gastrointestinal tract of rainbow trout
Toxicol. Appl. Pharmacol.
cDNA cloning and expression of a cytochrome P450 1A (CYP1A) gene from the hermaphroditic fish Rivulus marmoratus
Mar. Pollut. Bull.
Noncompetitive mixed-type inhibition of rainbow trout CYP1A catalytic activity by clotrimazole
Comp. Biochem. Physiol. C Pharmacol. Toxicol. Endocrinol.
Expression of cytochrome P450(11beta) (11beta-hydroxylase) gene during gonadal sex differentiation and spermatogenesis in rainbow trout, Oncorhynchus mykiss
J. Steroid Biochem. Mol. Biol.
Expression of a novel cytochrome P450 4T gene in rare minnow (Gobiocypris rarus) following perfluorooctanoic acid exposure
Comp. Biochem. Physiol. C Toxicol. Pharmacol.
Molecular characterization and sex-specific tissue expression of estrogen receptor alpha (esr1), estrogen receptor betaa (esr2a) and ovarian aromatase (cyp19a1a) in yellow perch (Perca flavescens)
Comp. Biochem. Physiol. B Biochem. Mol. Biol.
Aromatase immunoreactivity in the bluehead wrasse brain, Thalassoma bifasciatum: immunolocalization and co-regionalization with arginine vasotocin and tyrosine hydroxylase
Brain Res.
Induction of cytochromes P450 and mixed-function oxidase activity by polychlorinated biphenyls and beta-naphthoflavone in carp (Cyprinus carpio)
Comp. Biochem. Physiol. C
Cytochrome P4501A expression, chemical contaminants and histopathology in roach, goby and sturgeon and chemical contaminants in sediments from the Caspian Sea, Lake Balkhash and the Ily River Delta, Kazakhstan
Mar. Pollut. Bull.
Molecular cloning of CYP1A from the estuarine fish Fundulus heteroclitus and phylogenetic analysis of CYP1 genes: update with new sequences
Comp. Biochem. Physiol. C Pharmacol. Toxicol. Endocrinol.
Expression and characterization of cytochrome P450 2X1 in channel catfish (Ictalurus punctatus)
Biochim. Biophys. Acta
Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer
J. Biol. Chem.
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