CYP4A11 is repressed by retinoic acid in human liver cells

Antoun, Joseph; Amet, Yolande; Simon, Brigitte; Dréano, Yvonne; Corlu, Anne; Corcos, Laurent; Salaün, Jean‐Pierre; Plée-Gautier, Emmanuelle

doi:10.1016/j.febslet.2006.05.006

Cited by 23 publications

(14 citation statements)

References 43 publications

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“…Likewise, we observed that CYP4A11 expression was down-regulated in DMSO-treated cells. This supports the well established differential regulation of the human CYP4A genes, especially CYP4A11, which was shown to be regulated by retinoic acid, bezafibrate, and dexamethasone in human (Savas et al, 2003;Antoun et al, 2006).…”

Section: Steps Of Differentiationsupporting

confidence: 85%

CYP4F3B Expression Is Associated with Differentiation of HepaRG Human Hepatocytes and Unaffected by Fatty Acid Overload

Madec¹,

Cérec²,

Plée-Gautier³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Fatty acid microsomal -oxidation involves cytochrome P450 enzymes. Some of them belonging to the CYP4F3 family are mainly expressed in the liver, making this organ a major player in energy homeostasis and lipid metabolism. To study this important regulation pathway, we used HepaRG cells, which gradually undergo a complete differentiation process. Even at the early stage of the differentiation process, CYP4F3B generated by alternative splicing of the CYP4F3 gene represented the prevalent isoform in HepaRG cells as in the liver. Its increasing expression associated with hepatocyte differentiation status suggested a hepatic-specific control of this isoform. As in liver microsomes, the catalytic hydroxylation of the CYP4F3B substrate [1-

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Section: Steps Of Differentiationsupporting

confidence: 85%

CYP4F3B Expression Is Associated with Differentiation of HepaRG Human Hepatocytes and Unaffected by Fatty Acid Overload

Madec¹,

Cérec²,

Plée-Gautier³

et al. 2011

Drug Metab Dispos

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“…S3) (44-46). On the other hand, ATRA has been shown to be a strong inducer of CYP4Fs (32,33), while it suppressed expression of CYP4A11 (34). Upon treatment with ATRA, we observed a more than 2-fold increase in the downstream metabolites, suggesting that CYP4F rather than CYP4A enzymes are involved.…”

Section: The Downstream Metabolism Of 1-deoxyso Is Mediated By Cyp4f mentioning

confidence: 55%

“…As HET0016 inhibits both CYP4A and CYP4F enzymes, we treated cells with all-trans retinoic acid (ATRA; 20 M), which preferentially induces the expression of CYP4F genes (32)(33)(34). ATRA treatment significantly increased all the d3-deoxySL downstream metabolites.…”

Section: The Metabolic Conversion Of 1-deoxysls Is Slow Compared Withmentioning

confidence: 99%

Cytotoxic 1-deoxysphingolipids are metabolized by a cytochrome P450-dependent pathway

Alecu¹,

Othman²,

Penno³

et al. 2017

Journal of Lipid Research

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This article is available online at http://www.jlr.org Sphingolipid (SL) de novo synthesis typically starts with the condensation of serine and palmitoyl-CoA, a reaction catalyzed by serine palmitoyltransferase (SPT) (1-3). SPT can also use alanine in certain conditions (4), which results in the formation of the atypical cytotoxic 1-deoxysphingolipids (1-deoxySLs). These lack the C1-hydroxyl group of regular SLs, which is essential for further metabolic steps and degradation (4, 5). As such, 1-deoxySLs are commonly believed to be "dead-end" metabolites that accumulate within cells, tissues, and body fluids.Pathologically elevated 1-deoxySLs have been found in a number of neurological and metabolic disorders. They are a hallmark of hereditary sensory autonomic neuropathy type 1 (HSAN1), a rare autosomal dominant inherited peripheral neuropathy that is caused by various mutations in SPT. Plasma 1-deoxySLs are also elevated in patients with nondiabetic metabolic syndrome (MetS) and T2D (6) and may contribute to the development of diabetic sensory polyneuropathy (DSN), which is clinically very similar to HSAN1 (7,8). Both conditions start in the lower extremities with a loss of sensation often accompanied by positive sensory symptoms such as hyperpathia and neuropathic pain, as well as the development of painless wounds leading to ulcers (9, 10). L-serine supplementation was shown to effectively lower 1-deoxySL levels while improving Abstract The 1-deoxysphingolipids (1-deoxySLs) are atypical sphingolipids (SLs) that are formed when serine palmitoyltransferase condenses palmitoyl-CoA with alanine instead of serine during SL synthesis. The 1-deoxySLs are toxic to neurons and pancreatic -cells. Pathologically elevated 1-deoxySLs cause the inherited neuropathy, hereditary sensory autonomic neuropathy type 1 (HSAN1), and are also found in T2D. Diabetic sensory polyneuropathy (DSN) and HSAN1 are clinically very similar, suggesting that 1-deoxySLs may be implicated in both pathologies. The 1-deoxySLs are considered to be dead-end metabolites, as they lack the C1-hydroxyl group, which is essential for the canonical degradation of SLs. Here, we report a previously unknown metabolic pathway, which is capable of degrading 1-deoxySLs. Using a variety of metabolic labeling approaches and high-resolution high-accuracy MS, we identified eight 1-deoxySL downstream metabolites, which appear to be formed by cytochrome P450 (CYP)4F enzymes. Comprehensive inhibition and induction of CYP4F enzymes blocked and stimulated, respectively, the formation of the downstream metabolites. Consequently, CYP4F enzymes might be novel therapeutic targets for the treatment of HSAN1 and DSN, as well as for the prevention of T2D. (I.A., A.O., T.H., and A.v.E.) Abbreviations: ATRA, all-trans retinoic acid; CYP, cytochrome P450; DB, double bond; 1-deoxySA, 1-deoxysphinganine; 1-deoxySAdiene, deoxysphingadiene; 1-deoxySA-OH, hydroxyl-deoxysphinganine; 1-deoxySA-2OH, dihydroxyl-deoxysphinganine; 1-deoxySL, 1-deoxysphingolipid; 1-deoxySO, 1-deoxysphingosi...

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“…After 12 days, the medium was supplemented at first with 1% DMSO and then with 2% DMSO until the 24th day, when the different treatments were applied, according to previous reports (26).…”

Section: Cell Culturementioning

confidence: 99%

“…Total RNA was extracted using the ABI Prism™ 6100 Nucleic Acid PrepStation (Applied Biosystems, Courtaboeuf, France) as described (26). The integrity of total RNA was checked on an Agilent 2100 Bioanalyser using the RNA 6000 Nano LabChip kit (Agilent Technologies, Palo Alto, CA).…”

Section: Rna Extraction and Quality Controlmentioning

confidence: 99%

CYP4F3B is induced by PGA1 in human liver cells: a regulation of the 20-HETE synthesis

Antoun

Goulitquer

Amet

et al. 2008

Journal of Lipid Research

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CYP4A11 is repressed by retinoic acid in human liver cells

Cited by 23 publications

References 43 publications

CYP4F3B Expression Is Associated with Differentiation of HepaRG Human Hepatocytes and Unaffected by Fatty Acid Overload

CYP4F3B Expression Is Associated with Differentiation of HepaRG Human Hepatocytes and Unaffected by Fatty Acid Overload

Cytotoxic 1-deoxysphingolipids are metabolized by a cytochrome P450-dependent pathway

CYP4F3B is induced by PGA1 in human liver cells: a regulation of the 20-HETE synthesis

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