Tissue Distribution of mRNA Expression of Human Cytochrome P450 Isoforms Assessedby High-Sensitivity Real-Time Reverse Transcription PCR

Nishimura, Masuhiro; Yaguti, Hiroshi; Yoshitsugu, Hiroki; Naito, Shinsaku; Satoh, Tetsuo

doi:10.1248/yakushi.123.369

Cited by 289 publications

(211 citation statements)

References 14 publications

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“…[55][56][57][58] CYP2C19, CYP2D6 and CYP3A4 are predominantly expressed in human liver. 59) On the other hand, there are species differences between monkeys and humans in the expression of CYP1A1. CYP1A1 is rarely expressed in the human liver, but CYP1A2 is constitutively expressed.…”

Section: Discussionmentioning

confidence: 99%

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Differentiation of Monkey Embryonic Stem Cells into Hepatocytes and mRNA Expression of Cytochrome P450 Enzymes Responsible for Drug Metabolism: Comparison of Embryoid Body Formation Conditions and Matrices

Momose

Matsunaga

Murai

et al. 2009

Biological & Pharmaceutical Bulletin

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Examination of drug metabolism using human hepatocytes is important in the early stages of drug development. However, primary human hepatocytes are short-lived and cannot be maintained in culture over the long term. Considerable donor-dependent variations are also problematic. Human embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts and are capable of differentiating into three embryonic germ layers and germ cells.1) The cells apparently differentiate into various types of mature cells, and are thereby an attractive source for routine access to large numbers of cells that can be used for the development of candidate drug-screening strategies replacing primary cells.2) However, ethical considerations have limited the availability of human ES cells. The phenotype of human ES cells is known to be similar to that of monkey ES cells but differs from that of mouse ES cells with regard to morphology, response to leukemia inhibitory factor, and gene expression patterns. 1,[3][4][5] Research using monkey ES cells is considered to be useful for investigation of differentiation mechanisms in primate ES cells and models of human ES cells. Recently, it has been shown that monkey ES cells can be differentiated into various cell types-including neurons, hematopoietic cells, and pancreatic cells-using growth factors. [6][7][8] Hepatocytes derived from monkey ES cells may be useful for pharmacokinetic examinations such as induction of drug metabolism enzymes and interactions of candidate drugs. To date however, there have been few reported studies describing the differentiation of monkey ES cells into hepatocytes. 9,10) After the emergence of the liver bud from the developing gut tube, the level of hepatic maturation is characterized by the expression of liver-and stage-specific genes. For example, alfa-fetoprotein (AFP) is an early hepatic marker, expressed by hepatoblasts in the liver bud until birth.11,12) The synthesis of AFP decreases dramatically after birth and only trace amounts are expressed in the adult liver. In contrast, albumin (ALB), the most abundant protein synthesized by hepatocytes, is initially expressed at lower levels in early fetal hepatocytes but this increases as the hepatocytes mature, reaching a maximum in adult hepatocytes. 13,14) The mRNA expression of cytochrome P450 7A1 (CYP7A1) which is a rate-limiting enzyme in the conversion of cholesterol to bile acids in liver 15) is detected in fetal liver of third trimester of pregnancy.16) After birth, CYP7A1 increases several-fold with age both at the enzyme activity level and the mRNA level. 17,18) The in vitro approaches involve the formation of embryoid bodies (EBs) to mimic the inductive microenvironment required for liver organogenesis [19][20][21] and treatment with specific growth factors and cytokines critical for hepatic differentiation.22) At present, culture systems for ES cells have mainly used gelatin-or collagen-coated plates as the matrix for the maintenance of cells in an undifferentiated state an...

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Section: Discussionmentioning

confidence: 99%

“…60) Furthermore, the expression level of CYP1A1 mRNA was much lower than that of CYP1A2 mRNA in the human liver. 59) However, the most of CYP1A enzyme expressed in cynomolgus monkey liver is CYP1A1. 61) CYP1A1 mRNA was constitutively expressed (Figs.…”

Section: Discussionmentioning

confidence: 99%

Differentiation of Monkey Embryonic Stem Cells into Hepatocytes and mRNA Expression of Cytochrome P450 Enzymes Responsible for Drug Metabolism: Comparison of Embryoid Body Formation Conditions and Matrices

Momose

Matsunaga

Murai

et al. 2009

Biological & Pharmaceutical Bulletin

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“…In humans, the predominant -hydroxylases in liver and kidney are microsomal P450s 4A11, 4F2, and 4F3B (4). The -hydroxylation of saturated fatty acids is generally associated with P450 4A enzymes in non-human species, and human P450 4A11 catalyzes the -hydroxylation of lauric acid Ͼ palmitic acid Ͼ arachidonic acid (5).…”

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confidence: 99%

Regulation of Human Cytochrome P450 4F2 Expression by Sterol Regulatory Element-binding Protein and Lovastatin

Hsu

Savas

Griffin

et al. 2007

Journal of Biological Chemistry

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The capacity to oxidize the terminal carbon of aliphatic chains is a highly conserved enzymatic activity of cytochrome P450s in plant and animal species. In mammals, the -hydroxylation of fatty acids provides a means to remove potentially toxic excess concentrations of free fatty acids. This is the first step in the formation of dicarboxylic acids that can be more readily excreted or are further degraded by peroxisomal ␤-oxidation. The -hydroxylases also provide pathways for the degradation of signaling molecules such as prostanoids and leukotrienes. On the other hand, -hydroxylation of arachidonic acid forms 20-hydroxyeicosatetraenoic acid (20-HETE), 2 which has been implicated in the regulation of vascular tone and blood pressure (1-3).Cytochrome P450 4F2 (P450 4F2) is a fatty acid -hydroxylase that is expressed in human liver and kidney and contributes to free fatty acid catabolism and the conversion of arachidonic acid to 20-HETE. In humans, the predominant -hydroxylases in liver and kidney are microsomal P450s 4A11, 4F2, and 4F3B (4). The -hydroxylation of saturated fatty acids is generally associated with P450 4A enzymes in non-human species, and human P450 4A11 catalyzes the -hydroxylation of lauric acid Ͼ palmitic acid Ͼ arachidonic acid (5). Selective disruption of the murine Cyp4a10 (6) and Cyp4a14 (7) genes leads to hypertensive phenotypes that are thought to reflect changes in renal 20-HETE production arising through distinct mechanisms. Interestingly, an allelic variant encodes a human CYP4A11 with reduced catalytic activity that is associated with an increased risk for hypertension in studies of three independent cohorts (8, 9). P450s 4F2 and 4F3B are highly similar in amino acid sequence and display overlapping catalytic activity profiles. Both enzymes efficiently oxidize arachidonic acid (10). An alternative transcript of the CYP4F3 gene, 4F3A, arises from differential promoter use leading to the incorporation of an alternative exon that alters substrate preferences to favor the -hydroxylation of leukotrienes (11). P450 4F3A is predominantly expressed in human leukocytes (12). Antibody inhibition experiments (13, 14) suggest that P450 4F2/4F3B in human liver and kidney microsomes contribute ϳ66% to the formation of 20-HETE. Recently, P450s 4F2 and 4F3B were found to -hydroxylate very long chain saturated fatty acids (15) as well as phytanic acid (16). Our preliminary experiments using com-* This work was supported by National Institutes of Health Grant HD004445(to E. F. J.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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“…The expression of CYP3A5 was reported in prostate and other extrahepatic tissues by a number of researchers using the RT-PCR methodology (Murray et al, 1995;Yamakoshi et al, 1999;Finnstrom et al, 2001;Nishimura et al, 2003). A more recent study reported the CYP3A5 expression in normal prostate cells but not in prostate cancer cells (Leskelä et al, 2007).…”

Section: Resultsmentioning

confidence: 98%

Detection of Cytochrome P450-2A6, -3A5 and -4B1 with Real-Time Polymerase Chain Reaction in Prostate Tissue

Zencir

Alptekin

Çeliktaş

et al. 2008

Zeitschrift Für Naturforschung C

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Cytochrome P450 (CYP) is a heme-containing enzyme superfamily metabolizing a wide variety of xenobiotics, including drugs and carcinogens. The majority of CYP genes are expressed in the liver, however, some CYP isoforms are also reported for a number of extra hepatic tissues. We analyzed Cytochrome P450Ð2A6, -3A5 and -4B1 mRNAs using realtime reverse-transcriptase polymerase chain reaction (RT-PCR) in a total of 21 homogenized prostate tissues with or without malignancy. We detected a consistent expression of CYP2A6 and CYP3A5 in all, and of CYP4B1 in some (11/21) of the samples at mRNA level. Neither the histopathological status nor the smoking habit of the individuals affected CYP4B1 expression. Our results reflect possible roles for these particular CYPs in therapy and protection of prostate tissue.

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Tissue Distribution of mRNA Expression of Human Cytochrome P450 Isoforms Assessedby High-Sensitivity Real-Time Reverse Transcription PCR

Cited by 289 publications

References 14 publications

Differentiation of Monkey Embryonic Stem Cells into Hepatocytes and mRNA Expression of Cytochrome P450 Enzymes Responsible for Drug Metabolism: Comparison of Embryoid Body Formation Conditions and Matrices

Differentiation of Monkey Embryonic Stem Cells into Hepatocytes and mRNA Expression of Cytochrome P450 Enzymes Responsible for Drug Metabolism: Comparison of Embryoid Body Formation Conditions and Matrices

Regulation of Human Cytochrome P450 4F2 Expression by Sterol Regulatory Element-binding Protein and Lovastatin

Detection of Cytochrome P450-2A6, -3A5 and -4B1 with Real-Time Polymerase Chain Reaction in Prostate Tissue

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