Liver-specific cytochrome P450 CYP2C22 is a direct target of retinoic acid and a retinoic acid-metabolizing enzyme in rat liver

Qian, Liying; Zolfaghari, Reza; Ross, A. Catharine

doi:10.1194/jlr.m002840

Cited by 30 publications

(45 citation statements)

References 55 publications

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“…While CYP2C8 is catalytically more effi cient than either CYP2C9 or CYP3A4, the overall contribution of CYP2C8 to atRA hydroxylation may not be much greater than that of CYP3A4 and CYP2C9, because the two latter enzymes are expressed at about 10-fold higher levels than CYP2C8 ( 139 ). Moreover, while the expression of both CYP2C8 and CYP2C9 genes is induced by atRA, CYP2C9 is signifi cantly more responsive to atRA treatment ( 144 ), which would further increase its contribution to atRA catabolism.…”

Section: Biosynthesis Of Atra From ␤ -Carotenementioning

confidence: 97%

“…The mouse homolog of this enzyme, CYP2C39, also exhibits atRA 4-hydroxylase activity ( 136 ). The rat CYP2C22, an ortholog of human CYP2C8 and CYP2C9, catabolizes atRA, and its expression is induced by vitamin A and exogenous RA through a canonical RA receptor-mediated mechanism, but the expression of CYP2C22 is essentially restricted to liver ( 144,148 ). Interestingly, under normal dietary con ditions, the relative level of CYP2C22 mRNA expression exceeds that of CYP26A1 by about 100-fold ( 148 ).…”

Section: Biosynthesis Of Atra From ␤ -Carotenementioning

confidence: 99%

“…In rodents, rat CYP2C7, rat CYP2C22, and mouse CYP2C39 may contribute to atRA catabolism ( 136,144,146 ). The rat CYP2C7 is atRA 4-hydroxylase, which is induced by dietary retinoids in vitamin A-defi cient mice ( 146,147 ).…”

Section: Biosynthesis Of Atra From ␤ -Carotenementioning

confidence: 99%

“…In addition to the three CYP26 enzymes, several members of other CYP families, including human CYP3A4, CYP3A5, CYP3A7, CYP1A1, CYP4A11, CYP2C8, CYP2C9, CYP2C22, CYP2C39, CYP2S1, and CYP2E1 (136)(137)(138)(139)(140)(141)(142)(143)(144)(145)(146)(147)(148)(149)(150), have been shown to catabolize atRA. While CYP2C8 is catalytically more effi cient than either CYP2C9 or CYP3A4, the overall contribution of CYP2C8 to atRA hydroxylation may not be much greater than that of CYP3A4 and CYP2C9, because the two latter enzymes are expressed at about 10-fold higher levels than CYP2C8 ( 139 ).…”

Section: Biosynthesis Of Atra From ␤ -Carotenementioning

confidence: 99%

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Enzymology of retinoic acid biosynthesis and degradation

Kedishvili

2013

Journal of Lipid Research

170

165

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This article is available online at http://www.jlr.org ( 10 ), and regulation of energy homeostasis ( 11,12 ). atRA exerts its actions by serving as an activating ligand of nuclear atRA receptors [retinoid acid receptor (RAR) ␣ , RAR ␤ , and RAR ␥ ] and peroxisome proliferator-activated receptors (PPAR) ␤ / ␦ , which form heterodimers with retinoid X receptors ( 13,14 ). The actions of the RARs are described in more detail in this thematic series by RochetteEgly and colleagues. The concentration of atRA during embryonic development is tightly controlled in a spatial and temporal manner, and in adult tissues, it is maintained within a very narrow range that is specifi c for each given tissue. If the control mechanisms fail and the concentration of atRA exceeds or falls below the optimal range, tissues and cells undergo pathophysiological changes that in most severe cases can lead to disease. Thus, the maintenance of optimal atRA levels is essential for life. This review focusses on recent fi ndings regarding the mechanisms that control atRA homeostasis, with specifi c emphasis on the enzymes involved in atRA biosynthesis and degradation. All-trans -retinoic acid (atRA) is a highly potent derivative of vitamin A that is required for virtually all essential physiological processes and functions because of its involvement in transcriptional regulation of over 530 different genes ( 1, 2 ). For example, atRA is necessary for differentiation and development of fetal and adult tissues, stem cell differentiation, and apoptosis ( 3-7 ), and for support of reproductive functions ( 8, 9 ), immune response

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Section: Biosynthesis Of Atra From ␤ -Carotenementioning

confidence: 97%

Section: Biosynthesis Of Atra From ␤ -Carotenementioning

confidence: 99%

Section: Biosynthesis Of Atra From ␤ -Carotenementioning

confidence: 99%

Section: Biosynthesis Of Atra From ␤ -Carotenementioning

confidence: 99%

See 2 more Smart Citations

Enzymology of retinoic acid biosynthesis and degradation

Kedishvili

2013

Journal of Lipid Research

170

165

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“…Excessive retinoic acid signalling in the liver is expected due to the interference of glyphosate with liver CYP enzymes [11,157,158], because the CYP2C gene family is needed to metabolize retinoic acid in the liver [159]. The action of retinoic acid is likely mediated through sonic hedgehog signalling [160].…”

Section: Colon and Liver Cancermentioning

confidence: 99%

Glyphosate, pathways to modern diseases IV: cancer and related pathologies

Samsel¹,

Seneff²

2015

JBPC

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Insulin induces human acyl‐coenzyme A: cholesterol acyltransferase1 gene expression via MAP kinases and CCAAT/enhancer‐binding protein α

Zhai

Cheng

et al. 2013

J of Cellular Biochemistry

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Insulin resistance characterized by hyperinsulinemia is associated with increased risk of atherosclerosis. Acyl-coenzyme A: cholesterol acyltransferase (ACAT) is an intracellular enzyme involved in cellular cholesterol homeostasis and in atherosclerotic foam cell formation. To investigate the relationship between hyperinsulinemia and atherosclerosis, we investigated whether insulin induced ACAT1 gene expression and found that insulin up-regulated ACAT1 mRNA, protein and enzyme activity in human THP-1 cells and THP-1-derived macrophages. Moreover, luciferase assays revealed that insulin enhanced the ACAT1 gene P1 promoter activity but not the P7 promoter. To explore the molecular mechanisms involved, deletion analysis of the human ACAT1 P1 promoter revealed an insulin response element (IRE) upstream of the P1 promoter (from -603 to -580), EMSA experiments demonstrated that CCAAT/enhancer binding protein α(C/EBPα) bound to the P1 promoter IRE. Insulin-induced ACAT1 upregulation was blocked by the presence of PD98059 (an inhibitor of extracellular signal-regulated kinase, ERK) and SB203580 (an inhibitor of p38 mitogen-activated protein kinase, p38MAPK) but not by Wortmannin (an inhibitor of phosphatidylinositol 3-kinase, PI3K) or U73122 (an inhibitor of phospholipase C-γ, PLCγ). These studies demonstrate that insulin promotes ACAT1 gene expression at the transcriptional level. The molecular mechanism of insulin action is mediated via interaction of the functional IRE upstream of the ACAT1 P1 promoter with C/EBPα and is MAPK-dependent.

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Liver-specific cytochrome P450 CYP2C22 is a direct target of retinoic acid and a retinoic acid-metabolizing enzyme in rat liver

Cited by 30 publications

References 55 publications

Enzymology of retinoic acid biosynthesis and degradation

Enzymology of retinoic acid biosynthesis and degradation

Glyphosate, pathways to modern diseases IV: cancer and related pathologies

Insulin induces human acyl‐coenzyme A: cholesterol acyltransferase1 gene expression via MAP kinases and CCAAT/enhancer‐binding protein α

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