CYP4A : Roles, Expression, and Clinical Impacts

Main Article Content

Nathaphon Kuncharoenwirat
Kanokwan Jarukamjorn

Abstract

Cytochrome P450 4A enzyme (CYP4A) plays an important role in w/w-1 hydroxylation of fatty acids (FA). w-Hydroxylation of arachidonic acid via CYP4A results in 20-hydroxyeicosatetraenoic acid (20-HETE), which is a potent vasoconstriction agent associated to cardiovascular disease. Hence, regulation of CYP4A expression is considered as a factor involved in the condition. Regarding the studies in rodents, regulatory expression of CYP4A is mediated by peroxisome proliferator activated receptor a (PPARa). After binding to a ligand, e.g. fibrates, plasticizers, and pesticides, the PPARa-ligand complex is formed and translocated to form a heterodimer with retinoid X receptor (RXR) in nucleus. The heterodimer bind with the specific base-sequences on peroxisome proliferator response element (PPRE) of CYP4A, followed by transcription of the gene. Nevertheless, this phenomenon does not occurred in human CYP4A, though human and rodents show very high percentage of base-sequences similarity. Regulatory mechanism of human CYP4A is presently unclear. Due to clinical reports, there is a relationship between polymorphism of human CYP4A and chronic diseases, e.g. diabetes retinopathy, abnormal lipid profile, and essential hypertension, etc. Therefore, this review focuses on significant role, expression, clinical impacts of CYP4A to be fundamental information for the study on regulation of human CYP4A expression and a guide to predict complications of chronic diseases associated CYP4A polymorphism.

Article Details

Section
Review Article

References

Bell DR, Plant NJ, Rider CG, et al. Species-specific induction of cytochrome P-450 4A RNAs: PCR cloning of partial guinea pig, human, and mouse CYP4A cDNAs. Biochem J 1993; 294(Pt 1): 173-180.

Bellamine A, Wang Y, Waterman MR, et al. Characterization of the CYP4A11 gene, a second CYP4A gene in humans. Arch Biochem Biophys 2003; 409(1): 221-227.

Bourne RR, Stevens GA, White RA, et al. Causes of vision loss worldwide, 1990-2010: a systematic analysis. Lancet Glob Health 2013; 1(6): e339-349.

Capdevila JH, Holla VR, Faick JR. Cytochrome P450 and the metabolism and bioactivation of arachidonic acid and eicosanoids. In: Ortiz de Montellano PR, editor. Cytochrome P450. 3rd ed. New York: Kluwer Academic/Plenum Publishers; 2005. 531-532.

Chapman MJ, Assmann G, Fruchart JC, Shepherd J, Sirtori C, European Consensus Panel on HDL-C. Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid --a position paper developed by the European Consensus Panel on HDL-C. Curr Med Res Opin 2004; 20(8): 1253-1268.

Chen P, Bonaldo P. Role of macrophage polarization in tumor angiogenesis and vessel normalization: implications for new anticancer therapies. Int Rev Cell Mol Biol 2013; 301: 1-35.

Chen XW, Yu TJ, Zhang J, et al. CYP4A in tumor-associated macrophages promotes pre-metastatic niche formation and metastasis. Oncogene 2017; 36(35): 5045-5057.

Cho BH, Park BL, Kim LH, Chung HS, Shin HD. Highly polymorphic human CYP4A11 gene. J Hum Genet 2005; 50(5): 259–263.

Corton JC, Anderson SP, Stauber A. Central role of peroxisome proliferator-activated receptors in the actions of peroxisome proliferators. Annu Rev Pharmacol Toxicol 2000; 40: 491-518.

Estabrook RW. A passion for P450s (remembrances of the early history of research on cytochrome P450). Drug Metab Dispos 2003; 31(12): 1461–1473.

Fan F, Muroya Y, Roman RJ. Cytochrome P450 eicosanoids in hypertension and renal disease. Curr Opin Nephrol Hypertens 2015; 24(1): 37-46.

Frisbee JC, Roman RJ, Falck JR, Krishna UM, Lombard JH. 20-HETE contributes to myogenic activation of skeletal muscle resistance arteries in Brown Norway and Sprague–Dawley rats. Microcirculation 2001; 8(1): 45-55.

Gainer JV, Bellamine A, Dawson EP, et al. Functional variant of CYP4A11 20-Hydroxyeicosatetraenoic acid synthase is associated with essential hypertension. Circulation 2005; 111(1): 63-69.

Graham RA, Goodwin B, Merrihew RV, Krol WL, LeCluyse EL. Cloning, tissue Expression, and regulation of beagle dog CYP4A genes. Toxicol Sci 2006; 92(2): 356-367.

Hiratsuka M, Nozawa H, Katsumoto Y, et al. Genetic polymorphisms and haplotype structures of the CYP4A22 gene in a Japanese population. Mutat Res 2006; 599(1-2): 98–104.

Honkakoski P, Negishi M. Regulation of cytochrome P450 (CYP) genes by nuclear receptors. Biochem J 2000; 347(Pt 2): 321-337.

Imig JD. Eicosanoid regulation of renal vasculature. Am J Physiol Renal Physiol 2000; 279(6): F965-F981.

Johnson EF, Hsu M, Savas U, Griffin KJ. Regulation of P450 4A expression by peroxisome proliferator activated receptors. Toxicology 2002; 181–182: 203–206.

Kawashima H, Naganuma T, Kusunose E, et al. Human fatty acid -hydroxylase, CYP4A11: Determination of complete genomic sequence and characterization of purified recombinant protein. Arch Biochem Biophys 2000; 378(2): 333-339.

Lino Cardenas CL, Renault N, Farce A, et al. Genetic polymorphism of CYP4A11 and CYP4A22 genes and in silico insights from comparative 3D modelling in a French population. Gene 2011; 487(1): 10–20.

Lundell K, Hansson R, Wikvall K. Cloning and expression of a pig liver taurochenodeoxycholic acid 6alpha-hydroxylase (CYP4A21): a novel member of the CYP4A subfamily. J Biol Chem 2001; 276(13): 9606-9612.

Lukaszewicz KM, Lombard JH. Role of the CYP4A/20-HETE pathway in vascular dysfunction of the Dahl salt-sensitive rat. Clin Sci (London) 2013; 124(12): 695-700.

Marji JS, Wamg M, Laniado-Schwartzman M. Cytochrome P-450 4A isoform expression and 20-HETE synthesis in renal preglomerular arteries. Am J Physiol Renal Physiol 2002; 283(1): F60–F67.

Martignoni M, Groothuis GM, de Kanter R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin Drug Metab Toxicol 2006; 2(6): 875-894.

Michalik L, Auwerx J, Berger JP, et al. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev 2006; 58(4): 726–741.

Mittal B, Tulsyan S, Kumar S, Mittal RD, Agarwal G. Cytochrome P450 in cancer susceptibility and treatment. In: Makowski GS, editor. Advances in clinical chemistry volume 71. Oxford: Elsevier Inc.; 2015. 79-83.

Nakamura MT, Cheon Y, Li Y, Nara TY. Mechanisms of regulation of gene expression by fatty acids. Lipids 2004; 39(11): 1077-1083.

Nelson DR, Zeldin DC, Hoffman SMG, Maltais LJ, Wain HM, Nebert DW. Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics 2004; 14(1): 1-18.

Nithipatikom K, Gross ER, Endsley MP, et al. Inhibition of Cytochrome P450-hydroxylase a novel endogenous cardioprotective pathway. Circ Res 2004; 95(8): e65-e71.

Ogino S, Gulley ML, den Dunnen JT, Wilson RB, Association for Molecular Patholpogy Training and Education Committtee. Standard mutation nomenclature in molecular diagnostics. J Mol Diagn 2007; 9(1): 1–6.

Palmer CNA, Hsu MH, Griffin KJ, Johnson EF. Novel sequence determinants in peroxisome proliferator signaling. J Biol Chem 1995; 270(27): 16114–16121.

Rettie AE, Kelly EJ. The CYP4 Family. In: Ioannides C, editor. Cytochromes P450: Role in the metabolism and toxicity of drug and other xenobiotics. Cambridge: The Royal Society of Chemistry; 2008. 385-394.

Roman RJ. P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiol Rev 2002; 82(1): 131–185.

Roman LJ, Palmer CN, Clark JE, et al. Expression of rabbit cytochromes P4504A which catalyze the omega-hydroxylation of arachidonic acid, fatty acids, and prostaglandins. Arch Biochem Biophys 1993; 307(1): 57-65.

Savas U, Hsu M, Johnson EF. Differential regulation of human CYP4A genes by peroxisome proliferators and dexamethasone. Arch Biochem Biophys 2003; 409(1): 212-220.

Sello MM, Jafta N, Nelson DR, et al. Diversity and evolution of cytochrome P450 monooxygenases in Oomycetes. Sci Rep 2015; 5: 11572.

Simpson AE. The Cytochrome P450 4 (CYP4) family. Gen Pharmacol 1997; 28(3): 351-359.

Stark K, Dostalek M, Guengerich FP. Expression and purification of orphan cytochrome P450 4X1 and oxidation of anandamide. FEBS J 2008; 275(14): 3706–3717.

Sugimoto K, Akasaka H, Katsuya T, et al. A polymorphism regulates CYP4A11 transcriptional activity and is associated with hypertension in a Japanese Population. Hypertension 2008; 52(6): 1142-1148.

Suzuki H, Kanno Y. Efficacy of can desartan on outcome in Saitama trial (E-COST) group: Effects of candesartan on cardiovascular outcomes in Japanese hypertensive patients. Hypertens Res 2005; 28(4):307–314.

Sun XF, Wang XJ, Yang YY. Association of CYP4A11 gene polymorphism with diabetic retinopathy in Chinese patients. Int J Clin Exp Med 2016; 9(9): 18346-18352.

Vogel F, Motulsky AG. Vogel and Motulsky's Human Genetics: Problems and approaches. 3rd ed. Heidelberg: Springer-Verlag Berlin Heidelberg; 1997. 58-60.

Wahli W, Braissant O, Desvergne B. Peroxisome proliferator activated receptors: Transcriptional regulators of adipogenesis, lipid metabolism and more. Chem Biol 1995; 2(5): 261-266.

Wang J, Singh H, Zhang F, et al. Endothelial dysfunction and hypertension in rats transduced with CYP4A2 adenovirus. Circ Res 2006; 98(7): 962-969.

Wang M, Brand-Schieber E, Zand BA, et al. Cytochrome P450-derived arachidonic acid metabolism in the rat kidney: Characterization of selective inhibitors. J Pharmacol Exp Ther 1998; 284(3): 966-973.

Wang Z, Yadav AS, Leskova W, Harris NR. Inhibition of 20-HETE attenuates diabetes-induced decreases in retinal hemodynamics. Exp Eye Res 2011; 93(1): 108-113.

White CC, Feng QP, Cupples LA, et al. CYP4A11 variant is associated with high density lipoprotein cholesterol in women. Pharmacogenomics J 2013; 13(1): 44–51.

Williams SN, Dunham E, Bradfield CA. Induction of Cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450 Structure, Mechanism, and Biochemistry. New York: Kluwer Academic/Plenum Publishers; 2005. 323-339.

Yoshinari K, Tien E, Negishi M, Honkakoski P. Receptor-mediated regulation of Cytochromes P450. In: Ioannides C, editor. Cytochromes P450: Role in the Metabolism and Toxicity of Drug and other Xenobiotics. Cambridge: The Royal Society of Chemistry; 2008. 418-439.

Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 2013; 138(1): 103-141.

Zhang H, Jin L, Mu T, et al. Associations of CYP4A11 gene–gene and gene–smoking interactions with essential hypertension in the male eastern Chinese Han population. Clin Exp Hypertens 2017; 39(5): 448–453.

Zhang Y, Klaassen CD. Hormonal regulation of Cyp4a isoforms in mouse liver and kidney. Xenobiotica 2013; 43(12): 1055–1063.