![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 30, Issue 10, 1108-1114, October 2002
Epidauros Biotechnologie AG, Bernried, Federal Republic of Germany
(I.K., R.We., E.H., L.W.); Dr. Margarete Fischer-Bosch-Institute of
Clinical Pharmacology, Stuttgart, Germany (R.Wo., O.B., M.E., U.Z.);
Department of Clinical Pharmacology, Georg-August University
Goettingen, Goettingen, Germany (J.B., L.W.); and Department of
Surgery, University Medical Center Charite, Berlin, Germany (A.N.,
P.N.)
The elucidation of the individual contributions of the four
CYP3A genes to the overall CYP3A activity has been
hampered by similarities in their sequence and function. We
investigated the expression of CYP3A mRNA species in the liver and in
various other tissues using gene-specific TaqMan probes. CYP3A4
transcripts were the most abundant CYP3A mRNA in each of the 63 white
European livers tested and accounted on average for 95% of the
combined CYP3A mRNA pool. CYP3A5 and CYP3A7 each contributed on average 2%, whereas CYP3A43 contributed 0.3% transcripts to this pool. Fourteen percent of livers exhibited an increased share of CYP3A5 transcripts (range 4-20%). These livers were either heterozygous for
the marker of the CYP3A5 polymorphism, the CYP3A5*1A allele, or
expressed very low levels of CYP3A4 mRNA. The CYP3A7 expression was
bimodal, and it was increased in 15% livers. CYP3A4 was the dominant
CYP3A in the intestine, followed by CYP3A5. CYP3A5 and CYP3A7, but not
CYP3A4, were also expressed in the adrenal gland and in the prostate,
whereas only CYP3A5 was detected in the kidney. These three tissues
were shown to express much lower levels of pregnane X receptor mRNA
than the intestine, indicating possibly a different mode of regulation
of CYP3A expression. Expression of CYP3A genes was undetectable in
peripheral blood lymphocytes. In summary, these assays and results
should aid in our efforts to further dissect the regulation and the
physiological and pharmacological significance of CYP3A isozymes.
This article has been cited by other articles:
|
|
 |
|
  K. Yasuda, A. Ranade, R. Venkataramanan, S. Strom, J. Chupka, S. Ekins, E. Schuetz, and K. Bachmann A Comprehensive in Vitro and in Silico Analysis of Antibiotics That Activate Pregnane X Receptor and Induce CYP3A4 in Liver and Intestine Drug Metab. Dispos., August 1, 2008; 36(8): 1689 - 1697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Ku, H.-J. Ahn, K.-A. Seo, H. Kim, M. Oh, S. K. Bae, J.-G. Shin, J.-H. Shon, and K.-H. Liu The Contributions of Cytochromes P450 3A4 and 3A5 to the Metabolism of the Phosphodiesterase Type 5 Inhibitors Sildenafil, Udenafil, and Vardenafil Drug Metab. Dispos., June 1, 2008; 36(6): 986 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Leskela, E Honrado, C Montero-Conde, I Landa, A Cascon, R Leton, P Talavera, J M Cozar, A Concha, M Robledo, et al. Cytochrome P450 3A5 is highly expressed in normal prostate cells but absent in prostate cancer Endocr. Relat. Cancer, September 1, 2007; 14(3): 645 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Biggs, J. Wan, N. S. Cutler, J. Hakkola, P. Uusimaki, H. Raunio, and G. S. Yost Transcription Factor Binding to a Putative Double E-Box Motif Represses CYP3A4 Expression in Human Lung Cells Mol. Pharmacol., September 1, 2007; 72(3): 514 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L. Nock, D. Tang, A. Rundle, C. Neslund-Dudas, A. T. Savera, C. H. Bock, K. G. Monaghan, A. Koprowski, N. Mitrache, J. J. Yang, et al. Associations between Smoking, Polymorphisms in Polycyclic Aromatic Hydrocarbon (PAH) Metabolism and Conjugation Genes and PAH-DNA Adducts in Prostate Tumors Differ by Race Cancer Epidemiol. Biomarkers Prev., June 1, 2007; 16(6): 1236 - 1245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-M. Moilanen, J. Hakkola, M. H. Vaarala, S. Kauppila, P. Hirvikoski, J. T. Vuoristo, R. J. Edwards, and T. K. Paavonen Characterization of androgen-regulated expression of CYP3A5 in human prostate Carcinogenesis, May 1, 2007; 28(5): 916 - 921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B. Eap, M. Bochud, R. C. Elston, P. Bovet, M. P. Maillard, J. Nussberger, L. Schild, C. Shamlaye, and M. Burnier CYP3A5 and ABCB1 Genes Influence Blood Pressure and Response to Treatment, and Their Effect Is Modified by Salt Hypertension, May 1, 2007; 49(5): 1007 - 1014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-l. Lin and P. F. Hollenberg The Inactivation of Cytochrome P450 3A5 by 17{alpha}-Ethynylestradiol Is Cytochrome b5-Dependent: Metabolic Activation of the Ethynyl Moiety Leads to the Formation of Glutathione Conjugates, a Heme Adduct, and Covalent Binding to the Apoprotein J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 276 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. O'Donnell, K. Grime, P. Courtney, D. Slee, and R. J. Riley The Development of a Cocktail CYP2B6, CYP2C8, and CYP3A5 Inhibition Assay and a Preliminary Assessment of Utility in a Drug Discovery Setting Drug Metab. Dispos., March 1, 2007; 35(3): 381 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gaedigk, D. W. Baker, R. A. Totah, R. Gaedigk, R. E. Pearce, C. A. Vyhlidal, D. C. Zeldin, and J. S. Leeder Variability of CYP2J2 Expression in Human Fetal Tissues J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 523 - 532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, X.-X. Yang, M. Huang, Z.-P. Hu, M. He, W. Duan, E. Chan, F.-S. Sheu, X. Chen, and S.-F. Zhou Small Interfering RNA-Mediated Silencing of Cytochrome P450 3A4 Gene Drug Metab. Dispos., September 1, 2006; 34(9): 1650 - 1657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Prueksaritanont, Y. Kuo, C. Tang, C. Li, Y. Qiu, B. Lu, K. Strong-Basalyga, K. Richards, B. Carr, and J. H. Lin In Vitro and in Vivo CYP3A64 Induction and Inhibition Studies in Rhesus Monkeys: A Preclinical Approach for CYP3A-Mediated Drug Interaction Studies Drug Metab. Dispos., September 1, 2006; 34(9): 1546 - 1555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. He, M. H. Court, D. J. Greenblatt, and L. L. von Moltke FACTORS INFLUENCING MIDAZOLAM HYDROXYLATION ACTIVITY IN HUMAN LIVER MICROSOMES Drug Metab. Dispos., July 1, 2006; 34(7): 1198 - 1207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Obligacion, M. Murray, and I. Ramzan Drug-Metabolizing Enzymes and Transporters: Expression in the Human Prostate and Roles in Prostate Drug Disposition J Androl, March 1, 2006; 27(2): 138 - 150. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Henningsson, S. Marsh, W. J. Loos, M. O. Karlsson, A. Garsa, K. Mross, S. Mielke, L. Vigano, A. Locatelli, J. Verweij, et al. Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 Polymorphisms with the Pharmacokinetics of Paclitaxel Clin. Cancer Res., November 15, 2005; 11(22): 8097 - 8104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fakhoury, C. Litalien, Y. Medard, H. Cave, N. Ezzahir, M. Peuchmaur, and E. Jacqz-Aigrain LOCALIZATION AND mRNA EXPRESSION OF CYP3A AND P-GLYCOPROTEIN IN HUMAN DUODENUM AS A FUNCTION OF AGE Drug Metab. Dispos., November 1, 2005; 33(11): 1603 - 1607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Busi and T. Cresteil CYP3A5 mRNA Degradation by Nonsense-Mediated mRNA Decay Mol. Pharmacol., September 1, 2005; 68(3): 808 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Leeder, R. Gaedigk, K. A. Marcucci, A. Gaedigk, C. A. Vyhlidal, B. P. Schindel, and R. E. Pearce Variability of CYP3A7 Expression in Human Fetal Liver J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 626 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. van Herwaarden, J. W. Smit, R. W. Sparidans, E. Wagenaar, C. M. M. van der Kruijssen, J. H. M. Schellens, J. H. Beijnen, and A. H. Schinkel MIDAZOLAM AND CYCLOSPORIN A METABOLISM IN TRANSGENIC MICE WITH LIVER-SPECIFIC EXPRESSION OF HUMAN CYP3A4 Drug Metab. Dispos., July 1, 2005; 33(7): 892 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. McCune, L. J. Risler, B. R. Phillips, K. E. Thummel, D. Blough, and D. D. Shen CONTRIBUTION OF CYP3A5 TO HEPATIC AND RENAL IFOSFAMIDE N-DECHLOROETHYLATION Drug Metab. Dispos., July 1, 2005; 33(7): 1074 - 1081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-l. Lin, U. M. Kent, and P. F. Hollenberg The Grapefruit Juice Effect Is Not Limited to Cytochrome P450 (P450) 3A4: Evidence for Bergamottin-Dependent Inactivation, Heme Destruction, and Covalent Binding to Protein in P450s 2B6 and 3A5 J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 154 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Lee, D. A. Bell, S. J. Coulter, B. Ghanayem, and J. A. Goldstein Recombinant CYP3A4*17 Is Defective in Metabolizing the Hypertensive Drug Nifedipine, and the CYP3A4*17 Allele May Occur on the Same Chromosome as CYP3A5*3, Representing a New Putative Defective CYP3A Haplotype J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 302 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Baker, R. H. N. van Schaik, L. P. Rivory, A. J. ten Tije, K. Dinh, W. J. Graveland, P. W. Schenk, K. A. Charles, S. J. Clarke, M. A. Carducci, et al. Factors Affecting Cytochrome P-450 3A Activity in Cancer Patients Clin. Cancer Res., December 15, 2004; 10(24): 8341 - 8350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zeigler-Johnson, T. Friebel, A. H. Walker, Y. Wang, E. Spangler, S. Panossian, M. Patacsil, R. Aplenc, A. J. Wein, S. B. Malkowicz, et al. CYP3A4, CYP3A5, and CYP3A43 Genotypes and Haplotypes in the Etiology and Severity of Prostate Cancer Cancer Res., November 15, 2004; 64(22): 8461 - 8467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Burk, I. Koch, J. Raucy, E. Hustert, M. Eichelbaum, J. Brockmoller, U. M. Zanger, and L. Wojnowski The Induction of Cytochrome P450 3A5 (CYP3A5) in the Human Liver and Intestine Is Mediated by the Xenobiotic Sensors Pregnane X Receptor (PXR) and Constitutively Activated Receptor (CAR) J. Biol. Chem., September 10, 2004; 279(37): 38379 - 38385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Schuetz Lessons from the CYP3A4 Promoter Mol. Pharmacol., February 1, 2004; 65(2): 279 - 281. [Full Text] [PDF]
|
|
|
|
|
|
G. Ghannam, A. Takeda, T. Camarata, M. A. Moore, A. Viale, and N. R. Yaseen The Oncogene Nup98-HOXA9 Induces Gene Transcription in Myeloid Cells J. Biol. Chem., January 9, 2004; 279(2): 866 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Williams, J. Cook, and S. I. Hurst A SIGNIFICANT DRUG-METABOLIZING ROLE FOR CYP3A5? Drug Metab. Dispos., December 1, 2003; 31(12): 1526 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Stevens, R. N. Hines, C. Gu, S. B. Koukouritaki, J. R. Manro, P. J. Tandler, and M. J. Zaya Developmental Expression of the Major Human Hepatic CYP3A Enzymes J. Pharmacol. Exp. Ther., November 1, 2003; 307(2): 573 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Lee, A. H. Conney, and B. T. Zhu Human Cytochrome P450 3A7 Has a Distinct High Catalytic Activity for the 16{alpha}-Hydroxylation of Estrone but not 17{beta}-Estradiol Cancer Res., October 1, 2003; 63(19): 6532 - 6536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Masuyama, Y. Hiramatsu, J.-i. Kodama, and T. Kudo Expression and Potential Roles of Pregnane X Receptor in Endometrial Cancer J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4446 - 4454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Givens, Y. S. Lin, A. L. S. Dowling, K. E. Thummel, J. K. Lamba, E. G. Schuetz, P. W. Stewart, and P. B. Watkins CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adults J Appl Physiol, September 1, 2003; 95(3): 1297 - 1300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Robertson, J. Field, B. Goodwin, S. Bierach, M. Tran, A. Lehnert, and C. Liddle Transgenic Mouse Models of Human CYP3A4 Gene Regulation Mol. Pharmacol., July 1, 2003; 64(1): 42 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Westlind-Johnsson, S. Malmebo, A. Johansson, C. Otter, T. B. Andersson, I. Johansson, R. J. Edwards, A. R. Boobis, and M. Ingelman-Sundberg COMPARATIVE ANALYSIS OF CYP3A EXPRESSION IN HUMAN LIVER SUGGESTS ONLY A MINOR ROLE FOR CYP3A5 IN DRUG METABOLISM Drug Metab. Dispos., June 1, 2003; 31(6): 755 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Yates, W. Zhang, P. Song, S. Li, A. O. Gaber, M. Kotb, M. R. Honaker, R. R. Alloway, and B. Meibohm The Effect of CYP3A5 and MDR1 Polymorphic Expression on Cyclosporine Oral Disposition in Renal Transplant Patients J. Clin. Pharmacol., June 1, 2003; 43(6): 555 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Hesse and M. H. Court Quantitation of CYP2B6, Constitutive Androstane Receptor, and Pregnane X Receptor mRNA levels Drug Metab. Dispos., May 1, 2003; 31(5): 685 - 685. [Full Text] [PDF]
|
|
|
|
|
|
R. J. Edwards, R. J. Price, P. S. Watts, A. B. Renwick, J. M. Tredger, A. R. Boobis, and B. G. Lake Induction of Cytochrome P450 Enzymes in Cultured Precision-Cut Human Liver Slices Drug Metab. Dispos., March 1, 2003; 31(3): 282 - 288. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
