Gene Symbol: Cyp4a1
Description: cytochrome P450, family 4, subfamily a, polypeptide 1
Alias: CYPIVA10, Cyp4a10, Cyp4a22, cytochrome P450 4A10, cytochrome P450, 4A1, cytochrome P450, 4a10, cytochrome P450, IVA1, cytochrome P450, family 4, subfamily A, polypeptide 22, cytochrome P450, family 4, subfamily a, polypeptide 10, cytochrome P450-LA-omega 1, cytochrome P452, lauric acid omega-hydroxylase, long-chain fatty acid omega-monooxygenase
Species: rat
Products:     Cyp4a1

Top Publications

  1. Hiratsuka M, Nozawa H, Katsumoto Y, Moteki T, Sasaki T, Konno Y, et al. Genetic polymorphisms and haplotype structures of the CYP4A22 gene in a Japanese population. Mutat Res. 2006;599:98-104 pubmed
    ..Among the isoforms of the CYP4A subfamily, the human CYP4A22 was recently identified...
  2. He X, Cryle M, De Voss J, de Montellano P. Calibration of the channel that determines the omega-hydroxylation regiospecificity of cytochrome P4504A1: catalytic oxidation of 12-HALODOdecanoic acids. J Biol Chem. 2005;280:22697-705 pubmed
    ..To test this hypothesis, the oxidation of 12-iodo-, 12-bromo-, and 12-chlorododecanoic acids by recombinant CYP4A1 has been examined...
  3. Stromstedt M, Hayashi S, Zaphiropoulos P, Gustafsson J. Cloning and characterization of a novel member of the cytochrome P450 subfamily IVA in rat prostate. DNA Cell Biol. 1990;9:569-77 pubmed
    ..In situ hybridization of rat kidney sections with PP1 showed that this P450 form is expressed in the outer stripe of the outer medulla, indicating its localization in the proximal tubules. ..
  4. Lukaszewicz K, Falck J, Manthati V, Lombard J. Introgression of Brown Norway CYP4A genes on to the Dahl salt-sensitive background restores vascular function in SS-5(BN) consomic rats. Clin Sci (Lond). 2013;124:333-42 pubmed publisher
    ..These findings indicate that SS rats have an up-regulation of the CYP4A/20-HETE pathway resulting in elevated ROS (reactive oxygen species) and reduced NO bioavailability causing vascular dysfunction. ..
  5. Wang J, Schmidt J, Roman R, Anjaiah S, Falck J, Lombard J. Modulation of vascular O2 responses by cytochrome 450-4A omega-hydroxylase metabolites in Dahl salt-sensitive rats. Microcirculation. 2009;16:345-54 pubmed publisher
    ..the HS diet and were unaffected by DDMS. These findings suggest that CYP450-4A enzymes contribute to resting tone and to an enhanced response to elevated PO(2) in arterioles of Dahl-SS rats fed the HS diet. ..
  6. Wang J, Maier K, Roman R, de la Cruz L, Zhu J, Henderson L, et al. Expression of cytochrome P450-4A isoforms in the rat cremaster muscle microcirculation. Microcirculation. 2004;11:89-96 pubmed
  7. Fan F, Geurts A, Murphy S, Pabbidi M, Jacob H, Roman R. Impaired myogenic response and autoregulation of cerebral blood flow is rescued in CYP4A1 transgenic Dahl salt-sensitive rat. Am J Physiol Regul Integr Comp Physiol. 2015;308:R379-90 pubmed publisher
    ..middle cerebral arteries (MCA), and autoregulation of CBF were compared in SS, SS-5(BN) rats and a newly generated CYP4A1 transgenic rat. 20-HETE production was 6-fold higher in cerebral arteries of CYP4A1 and SS-5(BN) than in SS rats...
  8. Dunn K, Renic M, Flasch A, Harder D, Falck J, Roman R. Elevated production of 20-HETE in the cerebral vasculature contributes to severity of ischemic stroke and oxidative stress in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2008;295:H2455-65 pubmed publisher
    ..This was associated with the elevated expression of cytochrome P-450 (CYP)4A protein and CYP4A1 and CYP4A8 mRNA...
  9. Hercule H, Wang M, Oyekan A. Contribution of cytochrome P450 4A isoforms to renal functional response to inhibition of nitric oxide production in the rat. J Physiol. 2003;551:971-9 pubmed
    ..Antisense oligonucleotides (ASODN) to CYP4A1, -4A2 and -4A3 reduced 20-HETE synthesis and downregulated the expression of CYP4A isoforms in renal microsomes...

More Information


  1. Pan J, Xiang Q, Renwick A, Price R, Ball S, Kao J, et al. Use of a quantitative real-time reverse transcription-polymerase chain reaction method to study the induction of CYP1A, CYP2B and CYP4A forms in precision-cut rat liver slices. Xenobiotica. 2002;32:739-47 pubmed
    ..2. Taqman primers and probe sets were developed for rat CYP1A1, CYP1A2, CYP2B1 and CYP4A1 forms. 3...
  2. Hercule H, Oyekan A. Renal cytochrome p450 oxygenases and preglomerular vascular response to arachidonic acid and endothelin-1 following ischemia/reperfusion. J Pharmacol Exp Ther. 2002;302:717-24 pubmed
  3. Hoch U, Ortiz de Montellano P. Covalently linked heme in cytochrome p4504a fatty acid hydroxylases. J Biol Chem. 2001;276:11339-46 pubmed
    ..Covalent binding has been demonstrated for CYP4A1, -4A2, -4A3, -4A8, and -4A11 heterologously expressed in Escherichia coli...
  4. Remmers E, Griffiths M, Longman R, Gulko P, Kawahito Y, Chen S, et al. An integrated rat genetic map: analysis of linkage conservation with the mouse and human maps. Transplant Proc. 1999;31:1549-54 pubmed
  5. Kroetz D, Huse L, Thuresson A, Grillo M. Developmentally regulated expression of the CYP4A genes in the spontaneously hypertensive rat kidney. Mol Pharmacol. 1997;52:362-72 pubmed
    ..b>CYP4A1 and CYP4A8 mRNA were detectable by 3 weeks of age and CYP4A2 mRNA at 5 weeks of age...
  6. Marji J, Wang 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:F60-7 pubmed
    ..metabolite in the microvasculature of the rat kidney formed primarily by the cytochrome P-450 (CYP) 4A isoforms, CYP4A1, CYP4A2, and CYP4A3...
  7. Li D, Xu H, Yang G, Yang J, Fang H, Tang J. Effects of rosuvastatin correlated with the down-regulation of CYP4A1 in spontaneously hypertensive rats. Microvasc Res. 2015;98:88-93 pubmed publisher
    ..The expression of CYP4A1 mRNA and protein in different tissues was detected by real-time PCR and Western blot...
  8. Vasudevan H, Yuen V, McNeill J. Testosterone-dependent increase in blood pressure is mediated by elevated Cyp4A expression in fructose-fed rats. Mol Cell Biochem. 2012;359:409-18 pubmed publisher
    ..Taken together our results suggest that in the presence of testosterone, the Cyp4A/20-HETE system plays a key role in elevating the blood pressure secondary to insulin resistance. ..
  9. Frisbee J, Lombard J. Parenchymal tissue cytochrome P450 4A enzymes contribute to oxygen-induced alterations in skeletal muscle arteriolar tone. Microvasc Res. 2002;63:340-3 pubmed
  10. Kawashima H, Naganuma T, Kusunose E, Kono T, Yasumoto R, Sugimura K, et al. Human fatty acid omega-hydroxylase, CYP4A11: determination of complete genomic sequence and characterization of purified recombinant protein. Arch Biochem Biophys. 2000;378:333-9 pubmed
    ..Although several reports from other groups described that CYP4A11 preparations catalyzed omega-hydroxylation of arachidonic acid, our purified recombinant protein exhibited no activity toward arachidonic acid nor prostaglandin A(1). ..
  11. Earnshaw D, Dale J, Goldfarb P, Gibson G. Differential splicing in the 3' non-coding region of rat cytochrome P-452 (P450 IVA1) mRNA. FEBS Lett. 1988;236:357-61 pubmed
    ..Northern blot analysis indicates that this is probably a consequence of differential splicing, which may be relevant to the tissue-specific regulation of this gene. ..
  12. Okita R, Okita J. Characterization of a cytochrome P450 from di(2-ethylhexyl) phthalate-treated rats which hydroxylates fatty acids. Arch Biochem Biophys. 1992;294:475-81 pubmed
    ..A polyclonal antibody to the P450DEHP recognized three protein bands in liver microsomes from control and DEHP-treated rats on Western blot analysis, but only two protein bands from phenobarbital-treated rats. ..
  13. Kimura S, Hanioka N, Matsunaga E, Gonzalez F. The rat clofibrate-inducible CYP4A gene subfamily. I. Complete intron and exon sequence of the CYP4A1 and CYP4A2 genes, unique exon organization, and identification of a conserved 19-bp upstream element. DNA. 1989;8:503-16 pubmed
    The P450 CYP4A1 and CYP4A2 genes were isolated from a rat genomic library constructed in the vector lambda EMBL3 and their complete sequences were determined...
  14. Ying C, Noguchi T, Aso H, Ikeda K, Yamori Y, Nara Y. The role of cytochrome p-450 in salt-sensitive stroke in stroke-prone spontaneously hypertensive rats. Hypertens Res. 2008;31:1821-7 pubmed publisher
    ..25% clofibrate and given a 1% NaCl solution for drinking water for 10 d. The expression levels of CYP4A1, 2C11, and 2C23 were measured by Western blotting...
  15. Wang M, Wang J, Chang H, Zand B, Jiang M, Nasjletti A, et al. Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats. Am J Physiol Renal Physiol. 2003;285:F295-302 pubmed
    ..However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats...
  16. Mayer B, Lieb W, Götz A, Konig I, Aherrahrou Z, Thiemig A, et al. Association of the T8590C polymorphism of CYP4A11 with hypertension in the MONICA Augsburg echocardiographic substudy. Hypertension. 2005;46:766-71 pubmed
    ..In contrast, we found no blood pressure-independent modulatory effect of CYP4A11 T8590C on cardiac size, structure, and function. ..
  17. Lukaszewicz K, Paudyal M, Falck J, Lombard J. Role of vascular reactive oxygen species in regulating cytochrome P450-4A enzyme expression in Dahl salt-sensitive rats. Microcirculation. 2016;23:540-548 pubmed publisher
    ..The CYP4A pathway plays a role in vascular dysfunction in SS rats and there appears to be a direct role of reduced NO availability due to salt-induced oxidant stress in upregulating CYP4A enzyme expression. ..
  18. Williams J, Sarkis A, Hoagland K, Fredrich K, Ryan R, Moreno C, et al. Transfer of the CYP4A region of chromosome 5 from Lewis to Dahl S rats attenuates renal injury. Am J Physiol Renal Physiol. 2008;295:F1764-77 pubmed publisher
    ..These results indicate that the introgression of the CYP4A genes from Lewis rats into the Dahl S rats increases the renal formation of 20-HETE and attenuates the development of hypertension and renal disease...
  19. LeBrun L, Hoch U, Ortiz de Montellano P. Autocatalytic mechanism and consequences of covalent heme attachment in the cytochrome P4504A family. J Biol Chem. 2002;277:12755-61 pubmed
    ..Mutation of the glutamic acid to an alanine in CYP4A1, CYP4A3, and CYP4A11 suppresses covalent heme binding...
  20. Nguyen X, Wang M, Reddy K, Falck J, Schwartzman M. Kinetic profile of the rat CYP4A isoforms: arachidonic acid metabolism and isoform-specific inhibitors. Am J Physiol. 1999;276:R1691-700 pubmed
    ..We have expressed high levels of the rat CYP4A1, -4A2, -4A3, and -4A8 cDNAs, using baculovirus and Sf 9 insect cells...
  21. Hardwick J, Song B, Huberman E, Gonzalez F. Isolation, complementary DNA sequence, and regulation of rat hepatic lauric acid omega-hydroxylase (cytochrome P-450LA omega). Identification of a new cytochrome P-450 gene family. J Biol Chem. 1987;262:801-10 pubmed
    ..Southern blot analysis indicates that this family contains two or three genes. ..
  22. Zhou Y, Huang H, Chang H, Du J, Wu J, Wang C, et al. Induction of renal 20-hydroxyeicosatetraenoic acid by clofibrate attenuates high-fat diet-induced hypertension in rats. J Pharmacol Exp Ther. 2006;317:11-8 pubmed
    ..Reverse transcription-polymerase chain reaction analysis showed that CYP4A1 and CYP4A8 expression was significantly decreased in the renal cortex of HF rats...
  23. Xu Y, Knipp G, Cook T. Expression of CYP4A isoforms in developing rat placental tissue and rat trophoblastic cell models. Placenta. 2005;26:218-25 pubmed, we have elucidated the temporal and spatial patterns of expression of the four known rat CYP4A isoforms (CYP4A1, CYP4A2, CYP4A3, and CYP4A8) in the junctional and labyrinthine zones of the developing rat chorioallantoic ..
  24. Park F, Sweeney W, Jia G, Akbulut T, Mueller B, Falck J, et al. Chronic blockade of 20-HETE synthesis reduces polycystic kidney disease in an orthologous rat model of ARPKD. Am J Physiol Renal Physiol. 2009;296:F575-82 pubmed publisher
    ..RT-PCR analysis indicated that the expression of CYP4A1, CYP4A2, CYP4A3, and CYP4A8 mRNA was increased two- to fourfold in cystic PCK compared with noncystic Sprague-..
  25. Jiang M, Mezentsev A, Kemp R, Byun K, Falck J, Miano J, et al. Smooth muscle--specific expression of CYP4A1 induces endothelial sprouting in renal arterial microvessels. Circ Res. 2004;94:167-74 pubmed
    ..We constructed adenoviruses expressing the CYP4A1 cDNA or LacZ under the control of the smooth muscle cell-specific promoter SM22alpha (Ad-SM22-4A1 and Ad-SM22-..