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Literatura académica sobre el tema "CYP4A11"

Autor: Grafiati

Publicado: 11 de marzo de 2023

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Artículos de revistas sobre el tema "CYP4A11"

Muller, Dominik N., Cosima Schmidt, Eduardo Barbosa-Sicard, Maren Wellner, Volkmar Gross, Hantz Hercule, Marija Markovic, Horst Honeck, Friedrich C. Luft y Wolf-Hagen Schunck. "Mouse Cyp4a isoforms: enzymatic properties, gender- and strain-specific expression, and role in renal 20-hydroxyeicosatetraenoic acid formation". Biochemical Journal 403, n.º 1 (13 de marzo de 2007): 109–18. http://dx.doi.org/10.1042/bj20061328.

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AA (arachidonic acid) hydroxylation to 20-HETE (20-hydroxyeicosatetraenoic acid) influences renal vascular and tubular function. To identify the CYP (cytochrome P450) isoforms catalysing this reaction in the mouse kidney, we analysed the substrate specificity of Cyp4a10, 4a12a, 4a12b and 4a14 and determined sex- and strain-specific expressions. All recombinant enzymes showed high lauric acid hydroxylase activities. Cyp4a12a and Cyp4a12b efficiently hydroxylated AA to 20-HETE with Vmax values of approx. 10 nmol·nmol−1·min−1 and Km values of 20–40 μM. 20-Carboxyeicosatetraenoic acid occurred as a secondary metabolite. AA hydroxylase activities were approx. 25–75-fold lower with Cyp4a10 and not detectable with Cyp4a14. Cyp4a12a and Cyp4a12b also efficiently converted EPA (eicosapentaenoic acid) into 19/20-OH- and 17,18-epoxy-EPA. In male mice, renal microsomal AA hydroxylase activities ranged between approx. 100 (NMRI), 45–55 (FVB/N, 129 Sv/J and Balb/c) and 25 pmol·min−1·mg−1 (C57BL/6). The activities correlated with differences in Cyp4a12a protein and mRNA levels. Treatment with 5α-dihydrotestosterone induced both 20-HETE production and Cyp4a12a expression more than 4-fold in male C57BL/6 mice. All female mice showed low AA hydroxylase activities (15–25 pmol·min−1·mg−1) and very low Cyp4a12a mRNA and protein levels, but high Cyp4a10 and Cyp4a14 expression. Renal Cyp4a12b mRNA expression was almost undetectable in both sexes of all strains. Thus Cyp4a12a is the predominant 20-HETE synthase in the mouse kidney. Cyp4a12a expression determines the sex- and strain-specific differences in 20-HETE generation and may explain sex and strain differences in the susceptibility to hypertension and target organ damage.

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HENG, Yee M., C. W. Sharon KUO, Paul S. JONES, Richard SAVORY, Ruth M. SCHULZ, Simon R. TOMLINSON, Tim J. B. GRAY y David R. BELL. "A novel murine P-450 gene, Cyp4a14, is part of a cluster of Cyp4a and Cyp4b, but not of CYP4F, genes in mouse and humans". Biochemical Journal 325, n.º 3 (1 de agosto de 1997): 741–49. http://dx.doi.org/10.1042/bj3250741.

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Genomic clones for Cyp4a12 and a novel member of the murine Cyp4a gene family were isolated. The novel gene, designated Cyp4a14, has a GC rich sequence immediately 5′ of the transcription start site, and is similar to the rat CYP4A2 and CYP4A3 genes. The Cyp4a14 gene spans approximately 13 kb, and contains 12 exons; sequence similarity to the rat CYP4A2 gene sequence falls off 300 bp upstream from the start site. In view of the known sex-specific expression of the rat CYP4A2 gene, the expression and inducibility of Cyp4a14 was examined. The gene was highly inducible in the liver when mice were treated with the peroxisome proliferator, methylclofenapate; induction levels were low in control animals and no sex differences in expression were observed. By contrast, the Cyp4a12 RNA was highly expressed in liver and kidney of control male mice but was expressed at very low levels in liver and kidney of female mice. Testosterone treatment increased the level of this RNA in female liver slightly, and to a greater extent in the kidney of female mice. In agreement with studies on the cognate RNA, expression of Cyp4a12 protein was male-specific in the liver of control mice and extremely high inducibility of Cyp4a10 protein, with no sex differences, was also demonstrated. In view of the overlapping patterns of inducibility of the three Cyp4a genes, we investigated whether the three genes were co-localized in the genome. Two overlapping yeast artificial chromosome (YAC) clones were isolated, and the three Cyp4a genes were shown to be present on a single YAC of 220 kb. The Cyp4a genes are adjacent to the Cyp4b1 gene, with Cyp4a12 most distant from Cyp4b1. The clustering of these two gene subfamilies in the mouse was replicated in the human, where the CYPA411 and CYP4B1 genes were present in a single YAC clone of 440 kb. However, the human CYP4F2 gene was mapped to chromosome 19. Phylogenetic analysis of the CYP4 gene families demonstrated that CYP4A and CYP4B are more closely related than CYP4F.

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Savas, Üzen, Daniel E. W. Machemer, Mei-Hui Hsu, Pryce Gaynor, Jerome M. Lasker, Robert H. Tukey y Eric F. Johnson. "Opposing Roles of Peroxisome Proliferator-activated Receptor α and Growth Hormone in the Regulation of CYP4A11 Expression in a Transgenic Mouse Model". Journal of Biological Chemistry 284, n.º 24 (14 de abril de 2009): 16541–52. http://dx.doi.org/10.1074/jbc.m902074200.

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CYP4A11 transgenic mice (CYP4A11 Tg) were generated to examine in vivo regulation of the human CYP4A11 gene. Expression of CYP4A11 in mice yields liver and kidney P450 4A11 levels similar to those found in the corresponding human tissues and leads to an increased microsomal capacity for ω-hydroxylation of lauric acid. Fasted CYP4A11 Tg mice exhibit 2–3-fold increases in hepatic CYP4A11 mRNA and protein, and this response is absent in peroxisome proliferator-activated receptor α (PPARα) null mice. Dietary administration of either of the PPARα agonists, fenofibrate or clofibric acid, increases hepatic and renal CYP4A11 levels by 2–3-fold, and these responses were also abrogated in PPARα null mice. Basal liver CYP4A11 levels are reduced differentially in PPARα−/− females (>95%) and males (<50%) compared with PPARα−/+ mice. Quantitative and temporal differences in growth hormone secretion are known to alter hepatic lipid metabolism and to underlie sexually dimorphic gene expression, respectively. Continuous infusion of low levels of growth hormone reduced CYP4A11 expression by 50% in PPARα-proficient male and female transgenic mice. A larger decrease was observed for the expression of CYP4A11 in PPARα−/− CYP4A11 Tg male mice to levels similar to that of female PPARα-deficient mice. These results suggest that PPARα contributes to the maintenance of basal CYP4A11 expression and mediates CYP4A11 induction in response to fibrates or fasting. In contrast, increased exposure to growth hormone down-regulates CYP4A11 expression in liver.

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LUNDELL, Kerstin. "Cloning and expression of two novel pig liver and kidney fatty acid hydroxylases [cytochrome P450 (CYP)4A24 and CYP4A25]". Biochemical Journal 363, n.º 2 (8 de abril de 2002): 297–303. http://dx.doi.org/10.1042/bj3630297.

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A new member of the cytochrome P450 (CYP) 4A subfamily (CYP4A21) was recently cloned by PCR from pig liver [Lundell, Hansson, and Wikvall (2001) J. Biol. Chem. 276, 9606–9612]. This enzyme does not catalyse ω- or (ω-1)-hydroxylation of lauric acid, the model substrate for CYP4A enzymes. Instead, CYP4A21 participates in bile acid biosynthesis in the pig. Extensive studies, primarily conducted to verify the aberrant amino acids found in CYP4A21 within a normally conserved CYP4A motif, revealed that besides CYP4A21 two additional sequences were co-amplified by PCR. These two sequences (designated CYP4A24 and CYP4A25), generated from both pig liver and kidney, were characterized by restriction-enzyme analysis and were subsequently cloned. The deduced amino acid sequences of CYP4A24 and CYP4A25 share extensive sequence identity (97%). Both enzymes, expressed in yeast cells, exhibit ω-and (ω-1)-hydroxylase activities towards lauric acid and palmitic acid. The positions of the variable regions between CYP4A24 and CYP4A25, which are confined to β-sheets 1 and 4, indicate a possible difference in substrate specificity or regioselectivity. The porcine CYP4A21, CYP4A24 and CYP4A25 enzymes, with an overall identity of 94%, have probably evolved from a common ancestral gene, perhaps in conjunction with species-specific habits.

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Wang, Mong-Heng, Hui Guan, Xuandai Nguyen, Barbara A. Zand, Alberto Nasjletti y Michal Laniado-Schwartzman. "Contribution of cytochrome P-450 4A1 and 4A2 to vascular 20-hydroxyeicosatetraenoic acid synthesis in rat kidneys". American Journal of Physiology-Renal Physiology 276, n.º 2 (1 de febrero de 1999): F246—F253. http://dx.doi.org/10.1152/ajprenal.1999.276.2.f246.

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20-Hydroxyeicosatetraenoic acids (20-HETE), a biologically active cytochrome P-450 (CYP) metabolite of arachidonic acid in the rat kidney, can be catalyzed by CYP4A isoforms including CYP4A1, CYP4A2, and CYP4A3. To determine the contribution of CYP4A isoforms to renal 20-HETE synthesis, specific antisense oligonucleotides (ODNs) were developed, and their specificity was examined in vitro in Sf9 cells expressing CYP4A isoforms and in vivo in Sprague-Dawley rats. Administration of CYP4A2 antisense ODNs (167 nmol ⋅ kg body wt−1 ⋅ day−1iv for 5 days) decreased vascular 20-HETE synthesis by 48% with no effect on tubular synthesis, whereas administration of CYP4A1 antisense ODNs inhibited vascular and tubular 20-HETE synthesis by 52 and 40%, respectively. RT-PCR of microdissected renal microvessel RNA indicated the presence of CYP4A1, CYP4A2, and CYP4A3 mRNAs, and a CYP4A1-immunoreactive protein was detected by Western analysis of microvessel homogenates. Blood pressure measurements revealed a reduction of 17 ± 6 and 16 ± 4 mmHg in groups receiving CYP4A1 and CYP4A2 antisense ODNs, respectively. These studies implicate CYP4A1 as a major 20-HETE synthesizing activity in the rat kidney and further document the feasibility of using antisense ODNs to specifically inhibit 20-HETE synthesis and thereby investigate its role in the regulation of renal function and blood pressure.

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Nguyen, Xuandai, Mong-Heng Wang, Komandla M. Reddy, John R. Falck y Michal Laniado Schwartzman. "Kinetic profile of the rat CYP4A isoforms: arachidonic acid metabolism and isoform-specific inhibitors". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 276, n.º 6 (1 de junio de 1999): R1691—R1700. http://dx.doi.org/10.1152/ajpregu.1999.276.6.r1691.

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20-Hydroxyeicosatetraenoic acid (HETE), the cytochrome P-450 (CYP) 4A ω-hydroxylation product of arachidonic acid, has potent biological effects on renal tubular and vascular functions and on the control of arterial pressure. We have expressed high levels of the rat CYP4A1, -4A2, -4A3, and -4A8 cDNAs, using baculovirus and Sf 9 insect cells. Arachidonic acid ω- and ω-1-hydroxylations were catalyzed by three of the CYP4A isoforms; the highest catalytic efficiency of 947 nM−1 ⋅ min−1for CYP4A1 was followed by 72 and 22 nM−1 ⋅ min−1for CYP4A2 and CYP4A3, respectively. CYP4A2 and CYP4A3 exhibited an additional arachidonate 11,12-epoxidation activity, whereas CYP4A1 operated solely as an ω-hydroxylase. CYP4A8 did not catalyze arachidonic or linoleic acid but did have a detectable lauric acid ω-hydroxylation activity. The inhibitory activity of various acetylenic and olefinic fatty acid analogs revealed differences and indicated isoform-specific inhibition. These studies suggest that CYP4A1, despite its low expression in extrahepatic tissues, may constitute the major source of 20-HETE synthesis. Moreover, the ability of CYP4A2 and -4A3 to catalyze the formation of two opposing biologically active metabolites, 20-HETE and 11,12-epoxyeicosatrienoic acid, may be of great significance to the regulation of vascular tone.

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Cho, Byeong Hoon, Byung Lae Park, Lyoung Hyo Kim, Hyun Sub Chung y Hyoung Doo Shin. "Highly polymorphic human CYP4A11 gene". Journal of Human Genetics 50, n.º 5 (mayo de 2005): 259–63. http://dx.doi.org/10.1007/s10038-005-0245-9.

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Bell, D. R., N. J. Plant, C. G. Rider, L. Na, S. Brown, I. Ateitalla, S. K. Acharya et al. "Species-specific induction of cytochrome P-450 4A RNAs: PCR cloning of partial guinea-pig, human and mouse CYP4A cDNAs". Biochemical Journal 294, n.º 1 (15 de agosto de 1993): 173–80. http://dx.doi.org/10.1042/bj2940173.

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PCR was used to demonstrate the presence of a conserved region and to clone novel members of the cytochrome P-450 4A gene family from guinea pig, human and mouse cDNAs. This strategy is based on the sequences at nucleotides 925-959 and at the haem binding domain (nucleotides 1381-1410) of the rat CYP4A1 gene. Murine Cyp4a clones showed high sequence identity with members of the rat gene family, but CYP4A clones from human and guinea pig were equally similar to the rat/mouse genes, suggesting that the rat/mouse line had undergone gene duplication events after divergence from human and guinea-pig lines. The mouse Cyp4a-12 clone was localized to chromosome 4 using interspecific backcross mapping, in a region of synteny with human chromosome 1. The assignment of the human CYP4A11 gene to chromosome 1 was confirmed by somatic cell hybridization. An RNAase protection assay was shown to discriminate between the murine Cyp4a-10 and Cyp4a-12 cDNAs. Treatment of mice with the potent peroxisome proliferator methylclofenapate (25 mg/kg) induced Cyp4a-10 RNA in liver, and to a lesser extent in kidney; there was no sex difference in this response. Cyp4a-12 RNA was present at high levels in male control liver and kidney samples, and was not induced by treatment with methylclofenapate. However, Cyp4a-12 RNA was present at low levels in control female liver and kidney RNA, and was greatly induced in both organs by methylclofenapate. Guinea pigs were exposed to methylclofenapate (50 mg/kg), but there was no significant induction of the guinea-pig CYP4A13 RNA. These findings are consistent with a species difference in response to peroxisome proliferators between the rat/mouse and the guinea pig.

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Elijovich, Fernando y Cheryl L. Laffer. "The relationship between CYP4A11 and human hypertension". Journal of Hypertension 26, n.º 8 (agosto de 2008): 1712–14. http://dx.doi.org/10.1097/hjh.0b013e3283000504.

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Yamaori, Satoshi, Noriyuki Araki, Kurumi Ikehata, Shigeru Ohmori y Kazuhito Watanabe. "Epalrestat potently and selectively inhibits CYP4A11 activity". Drug Metabolism and Pharmacokinetics 32, n.º 1 (enero de 2017): S55. http://dx.doi.org/10.1016/j.dmpk.2016.10.224.

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Más fuentes

Tesis sobre el tema "CYP4A11"

Lino, Cardenas Christian Lacks. "Identification et caractérisation du polymorphisme génétique des cytochromes P450 4A11 et 4A22 (CYP4A11 et CYP4A22) et de la glycine N-acyltransférase (GLYAT)". Phd thesis, Université du Droit et de la Santé - Lille II, 2010. http://tel.archives-ouvertes.fr/tel-00630109.

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Afin de s'adapter à son environnement chimique, l'organisme a développé au cours de l'évolution des systèmes enzymatiques capables de transformer de nombreuses molécules étrangères ou xénobiotiques (médicaments, composés toxiques, carcinogènes...), le plus souvent de nature hydrophobe, en métabolites suffisamment hydrophiles pour être plus facilement excrétés par voie urinaire et/ou biliaire. Certaines de ces enzymes sont également impliquées dans des processus cataboliques ou de biosynthèses de composés endogènes (acides gras, rétinoïdes, stéroïdes, prostaglandines...). Ces enzymes jouent ainsi un rôle fondamental à la fois dans la défense de l'organisme face à son environnement chimique et dans des processus physiologiques essentiels. On comprend dès lors que s'il existe, chez certains individus, des anomalies de séquence ou de structure des gènes codant pour ces enzymes, une partie de la population présentera une susceptibilité particulière à certaines molécules de l'environnement, voire des dysfonctionnements de certaines réactions biologiques indispensables. Les travaux de cette thèse s'inscrivent dans cette démarche. Dans un premier temps, ils ont consisté à évaluer la nature et l'étendue de la variabilité de la séquence nucléotidique de trois gènes codants pour les enzymes CYP4A11, CYP4A22 et la Glycine N-acyltransférase (GLYAT). Dans un deuxième temps, les analyses fonctionnelles des variations de séquence identifiées ont été abordées par des approches in silico et in vitro. Les cytochromes P450 CYP4A11 et CYP4A22, participent à la biotransformation de composés endogènes et sont impliqués plus particulièrement dans la voie d'activation de l'acide arachidonique. Des travaux récents suggèrent que des anomalies génétiques de ces enzymes constituent des facteurs de susceptibilité à l'hypertension artérielle chez l'homme. Nous avons ainsi analysé les variations de séquence du gène CYP4A11 et CYP4A22 dans des échantillons d'ADN provenant de volontaires sains. Au total, 26 polymorphismes ont été identifiés et 5 nouveaux CYP4A* allèles ont été caractérisés pour chaque isoforme CYP4A. Les structures 3D des protéines CYP4A ont été construites et validées pour l'analyse de l'impact des mutations identifiées. Bien que des travaux supplémentaires soient nécessaires pour confirmer le lien entre le polymorphisme génétique du CYP4A11 et du CYP4A22 et l'hypertension artérielle, ce travail représente la première description et caractérisation du polymorphisme génétique des isoformes CYP4A dans une population Française. De plus, nous avons mise en évidence une variabilité interethnique de ce polymorphisme génétique dans différentes populations testées. La glycine N-acyltransférase ou GLYAT est une enzyme impliquée dans la détoxication de xénobiotiques contenant un groupement carboxylique par conjugaison d'un résidu de glycine. Sept variations de séquence de la GLYAT ont été identifiées et quatre nouveaux GLYAT* allèles ont été caractérisés. La localisation des certaines mutations dans des structures secondaires très conservées de la protéine suggère un impact sur l'activité catalytique de cette enzyme. Bien que les conséquences cliniques potentielles de ces variations restent encore à étudier, ces résultats seront utiles pour de futures études d'association de ce polymorphisme génétique de la GLYAT avec les altérations de détoxications de xénobiotiques contenant un groupement carboxylique comme l'aspirine, certains pesticides ou le toluène.

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Bulsara, Daksha. "The effects of Poly IC and human interferon #alpha# on rat hepatic CYP4A1 and CYP2E1". Thesis, University of Surrey, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334347.

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Parmentier, Jean-Hugues. "Répression des cytochromes P450 par les Interleukines-1 et 6 : contrôle de l'expression du CYP4A1". Nancy 1, 1995. http://www.theses.fr/1995NAN10455.

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Baer, Brian R. "Autocatalytic mechanism and functional consequences of covalent heme attachment in CYP4B1 /". Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/8176.

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Graham, Richard Alan LeCluyse Edward L. "Biochemical and molecular characterization of beagle dog CYP4A". Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2006. http://dc.lib.unc.edu/u?/etd,290.

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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2006.
Title from electronic title page (viewed Oct. 10, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the School of Pharmacy." Discipline: Pharmacy; Department/School: Pharmacy.

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Hood, Steven Richard. "Isolation and characterisation of a human CYP4A gene". Thesis, University of Surrey, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359859.

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Kacher, Radhia. "Role of the cholesterol hydroxylase enzyme CYP46A1 in cholesterol metabolism and neuroprotection in Huntington's disease". Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS154.

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La maladie de Huntington (MH) est une maladie génétique autosomique dominante, causée par une augmentation du nombre de CAG sur le gène de la huntingtin. L’homéostasie du cholestérol cérébral est altérée dans la MH. L’expression de CYP46A1, enzyme neuronale catabolisant le cholestérol dans le cerveau, est diminuée dans le putamen des patients et dans le striatum de souris modèles de la MH. Après restauration de l’expression de CYP46A1 dans le striatum des souris Knock-In zQ175, les capacités locomotrices sont améliorées, l’agrégation de la huntingtine mutée est diminuée, l’atrophie neuronale est limitée et le métabolisme du cholestérol est stimulé. Une nouvelle signature transcriptionnelle est induite par CYP46A1, avec une restauration des voies impliquées dans l'autophagie, le protéasome, la communication synaptique et le transport axonal, connues pour leur dysfonctionnement dans la MH. CYP46A1 améliore la transmission synaptique et augmente la densité en épines synaptiques. L'élimination des agrégats par autophagie et par le protéasome est augmentée avec CYP46A1. Enfin, le transport de BDNF et de TrkB est amélioré par CYP46A1 dans un modèle in vitro de la MH. Ces résultats révèlent l'effet pléiotrope et bénéfique de la régulation du métabolisme du cholestérol dans la MH. Pour approfondir cette étude, une technique de tri cellulaire a été mise au point, afin de séparer les neurones et les astrocytes à partir de striatum de souris, pour étudier les régulations transcriptomique et lipidomique de ces deux populations. Cette étude permettra d’identifier de nouvelles cibles impliquées dans la neuroprotection par CYP46A1 et présentant un intérêt thérapeutique dans la MH
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by abnormal CAG expansion on huntingtin’s gene. Recently, altered brain cholesterol homeostasis has been implicated in HD. Particularly, the expression of CYP46A1, the rate-limiting enzyme for cholesterol degradation in the brain, is decreased in patients’ putamen and in the striatum of HD mouse models. We restored CYP46A1 expression into the striatum of the zQ175 mice. Behavioral, neuropathological and molecular tests were performed and showed an improvement of locomotor activity and histological landmarks. Cholesterol homeostasis was restored with an increase of cholesterol degradation and synthesis. CYP46A1 induced a new transcriptional signature, with restoration of pathways involved in autophagy, proteasome, synaptic communication and axonal transport, which are known to be dysfunctional in HD. CYP46A1 improved synaptic transmission and spine density in the striatum of the zQ175 mice. Aggregate clearance mediated by autophagy and proteasome was increased after CYP46A1 expression. Finally, BDNF and TrkB transport were enhanced by CY46A1 in HD in vitro models. Overall, CYP46A1 restoration alleviates the zQ175 pathological phenotype through a global compensation. To gain further insights into CYP46A1 neuroprotection, a cell sorting strategy was set up to study the transcriptomic and lipidomic signature in purified neurons and astrocytes. This method will lead to a greater understanding of cell-type-specific regulations and cell communication. Altogether, this project gave new insights into the potential application of CYP46A1 restoration as a therapeutic strategy in HD

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Heng, Yee M. "Genomic cloning and identification of a novel murine Cyp4a gene". Thesis, University of Nottingham, 1997. http://eprints.nottingham.ac.uk/10399/.

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The mouse cytochrome P450 4a family of genes is poorly characterised. This thesis describes a detailed study of these genes. Using primers derived from exon 1 of the mouse cyp3a10 cDNA sequence, a 1.4kb genomic fragment was cloned which contained the promoter region of the gene. Additionally, a lambda genomic library was screened with probes derived from the partial cDNA clones of the mouse cyp4a10 and cyp4a12. Originally, two classes of phage lambda clones were isolated. One clone, lambda 16, was partially sequenced and was found to contain the 3' end of the cyp4a12 gene. The second clone, lambda 4, was subcloned and found to be distinct from previously known murine cyp4a genes. This novel gene has been designated cyp4a14. To obtain the full cyp4a14 gene, the genomic library was rescreened. Lambda clone 12 was subsequently isolated from the library, which was found to contain exons 1 to 5 of Cyp4a14. In order to study the promoter region of cyp4a14, a pcr-based approach was undertaken to clone 4.4 kb upstream of exon 1 of the gene and a 1.2kb fragment has been sequenced. Cyp4a14 RNA was also found to be highly induced by a peroxisome proliferator, methylclofenapate. Primer extension analyses were performed to determine the start of transcription of Cyp4a14, which was mapped to a single T nucleotide 26bp upstream of the putative start site of protein translation. The promoter region of Cyp4a14 is highly similar to the corresponding regions of the rat CYP4A2 genes. however, similarity is dramatically reduced about 350bp upstream of the start of transcription, which coincides with the presence of two 358bp repeats in teh CYP4A2 gene. The promoter also contains a highly conserved 19bp element which is also found in the promoter regions of the CYP4A1 and CYP4A2 genes. Cyp4a14 is a novel member of the murine Cyp4a subfamily. It contains 12 exons and is highly similar to the rat CYP4A2/3 genes. However, there is high conservation in exon 3 between Cyp4a14 and cyp4a3, which makes it marginally more related to this gene. In addition, cyp4a14 shows very high similarity in exons 4,8, 11 and 12 with other known CYP4A genes. Correspondingly, the peptide sequences encoded by these exons are highly conserved. Exon 8 encodes a 16 amino acid motif, LRAEVDTFMGEGHDTT, which is highly conserved in the CYP4 family. Exons 22 and 12 encode the well known RNCIG motif, containing the haem-binding domain, which is the proposed signature for a P450 protein. Exon 4 in the CYP4A genes encodes for a highly conserved, but previously unreported motif, HRRMLLTPGFHYDIL. Primary sequence alignments indicate that these motifs map very close to or within predicted substrate recognition sites and thus could have an important role in the enzyme activities of the CYP4A enzyme. The identification of Cyp4a14 also enables the analysis of the evolution of the murine Cyp4a subfamily. The mouse has 4 genes in the Cyp4a subfamily; however, the closely related rat has four CYP4A members. As the rat CYP4A2, which is very similar to CYP4AA3, was not to have a homologue in the mouse, it must have arisen after the mouse lineage had diverged from the rat in evolutionary history. As all three mouse Cyp4a genes are significantly more similar to their equivalents in the rat than to other murine Cyp4a genes, the gene duplication events giving rise to these three genes must have occurred before the mouse had diverged from the rat. Phylogenetic analyses of the CYP4A, CYP4B and CYp4F subfamilies demonstrate that CYP4A genes are more similar to the CYP4B family than to the CYP4F subfamily. This suggests that the gene duplication event giving rise to the CYP4A and CYP4B genes must be a more recent event than that giving rise to the CYP4F subfamily. In addition, the CYP4A subfamily of genes is more divergent than the CYP4B subfamily across species.

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Fourgeux, Cynthia. "Cholestérol-24S-hydroxylase (CYP46A1) et homéostasie du cholestérol dans la rétine en conditions physiologiques et pathologiques". Phd thesis, Université de Bourgogne, 2012. http://tel.archives-ouvertes.fr/tel-00905888.

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Le cholestérol est le principal stérol présent dans la rétine. Dans sa forme libre, le cholestérol est distribué dans toutes les couches cellulaires de la rétine, alors que le cholestérol estérifié s'accumule essentiellement à la base de l'épithélium pigmentaire rétinien. La capacité intrinsèque de la rétine à synthétiser le cholestérol paraît limitée, ce qui implique nécessairement que des voies extra-rétiniennes participent activement à suppléer la rétine en cholestérol. Les cellules gliales de Müller contribueraient à l'apport de cholestérol aux neurones de la rétine, en particulier pour la formation des synapses. Les conséquences délétères d'une accumulation ou à l'inverse d'un déficit en cholestérol dans les neurones sur leur survie souligne l'importance de maintenir l'équilibre entre l'apport et la néosynthèse du cholestérol d'une part et son élimination d'autre part. Pour cela, la rétine neurale a en particulier la capacité de convertir, pour l'éliminer, le cholestérol en 24S-hydroxycholestérol. En effet, le transport du 24S-hydroxycholestérol au travers des membranes est facilité par la présence d'un groupe hydroxyle supplémentaire, lui conférant une polarité plus importante par rapport au cholestérol. L'enzyme qui catalyse cette réaction est la cholestérol-24S-hydroxylase (CYP46A1). Des liens ont été établis entre CYP46A1, 24S-hydroxycholestérol et processus neurodégénératifs dans le cerveau, suggérant un rôle potentiel dans certaines pathologies comme la maladie d'Alzheimer. CYP46A1 est exprimée dans la rétine neurale, et plus particulièrement dans les cellules ganglionnaires de la rétine. Le rôle de CYP46A1 dans la rétine reste pour l'instant inconnu. Cependant, par analogie avec le cerveau, nous pouvons supposer une fonction dans le contrôle de l'homéostasie du cholestérol dans les neurones et envisager une association avec des pathologies dégénératives de la rétine comme la Dégénérescence Maculaire Liée à l'Âge (DMLA) ou le glaucome. Dans ce contexte, l'objectif de nos travaux a consisté à évaluer le rôle de la cholestérol-24S-hydroxylase dans la rétine en conditions physiologiques et pathologiques. Par une approche clinique, nous avons trouvé qu'un polymorphisme génétique dans CYP46A1 était un facteur de risque de glaucome (Risque relatif=1,26, intervalle de confiance à 95%=1,006-1,574, p<0,05) (Fourgeux et al. 2009, Invest Ophthalmol Vis Sci 50:5712-7). Par contre, ce polymorphisme génétique n'a pas été retrouvé, en tant que tel, comme facteur de risque chez des patients DMLA, mais pourrait l'être chez les patients non porteurs d'allèles à risque dans les gènes CFH et LOC388715 (Fourgeux et al. 2012, Invest Ophthalmol Vis Sci 53:7026-33). Deux approches expérimentales nous ont permis de suggérer qu'il existe un lien entre le stress des cellules de la rétine et le 24S-hydroxycholestérol. En effet, dans une étude in vivo faite chez le rat, après avoir reproduit une caractéristique principale du glaucome par l'augmentation de la pression intraoculaire, nous avons suggéré le rôle crucial de la glie dans le maintien de l'expression de CYP46A1 au cours de la neurodégénérescence de la rétine (Fourgeux et al. 2012, Acta Ophthalmol, Sep 23 ; doi: 10.1111/j.1755-3768.2012.02490.x.). Enfin, l'inhibition pharmacologique de l'activité CYP46A1 dans la rétine par le voriconazole injecté in vivo chez le rat nous a permis de mettre en évidence que la diminution du contenu en 24S-hydroxycholestérol de la rétine était associée à une dysfonction des cellules ganglionnaires, évaluée par électrorétinographie. En parallèle, nous avons observé une activation gliale, dont l'amplitude était amplifiée par l'inhibition de l'activation microgliale induite par la minocycline [...]

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Simpson, AnneMarie Elizabeth Claire Merryman. "The ontogeny of cytochrome P450 4A (CYP4A) gene expression in the rat". Thesis, University of Leicester, 1994. http://hdl.handle.net/2381/34231.

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Cytochrome P450s (P450s) play a major role in the metabolism of endogenous and exogenous chemicals. P450-metabolism generally converts compounds into more hydrophilic derivatives, which can then be excreted. In contrast, it can lead to the formation of reactive intermediates, which can attack cellular macromolecules leading to mutagenesis. The cytochrome P450 4A (CYP4A) subfamily encodes proteins involved in lipid metabolism. The CYP4A1, CYP4A2 and CYP4A3 genes are expressed constitutively in the adult rat, elevated expression being seen after administration of a hypolipidemic drug, clofibrate. The interest in the CYP4A subfamily is partly related to the apparent close association between CYP4A1 induction and the phenomenon of sustained peroxisome proliferation. It is also believed that the CYP4A proteins may be involved in the production of physiologically important renal metabolites. The aim of this thesis was a systematic study of the ontogeny and inducibility of CYP4A1 mRNA and protein levels in embryonic, fetal and post-natal rats. Constitutive and induced hepatic expression of the CYP4A1, CYP4A2 and CYP4A3 mRNAs was demonstrated in the 24 day, 10.5 day and day 1 neonates, in addition to the 18.5 day fetal expression. Renal expression was not detected prenatally, and was only apparent in the day 1 neonates following induction. The mRNAs were also present in induced adult brown fat; induced and control adult and 24 day neonatal small intestine; induced 18.5 day fetal placenta and, induced and control 11.5 day embryonic decidua. The demonstration of inducible CYP4A1 gene expression is potentially important, as in conjunction with peroxisome proliferation, it may result in an increased susceptibility of the tissue to carcinogenesis. The P450 inductive response may also play an important role in elevating the rate of metabolism of foreign compounds to detoxified forms, or in some cases to harmful reactive intermediates. If this were to occur during pregnancy it could potentially have important consequences for the developing embryo/fetus.

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Libros sobre el tema "CYP4A11"

Bylund, Johan. Cytochrome P450 Enzymes in Oxygenation of Prostaglandin Endoperoxides & Arachidonic Acid: Cloning, Expression & Catalytic Properties of Cyp4F8 & Cyp4F21 ... from the Faculty of Pharmacy, 231). Uppsala Universitet, 2000.

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Capítulos de libros sobre el tema "CYP4A11"

Rainov, Nikolai G., M. Sena-Esteves, C. Fraefel, K. U. Dobberstein, E. A. Chiocca y X. O. Breakefield. "A Chimeric Fusion Protein of Cytochrome CYP4B1 and Green Fluorescent Protein for Detection of Pro-Drug Activating Gene Delivery and for Gene Therapy in Malignant Glioma". En Advances in Experimental Medicine and Biology, 393–403. Boston, MA: Springer US, 1998. http://dx.doi.org/10.1007/978-1-4615-5357-1_61.

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Hardwick, James P. "[26] CYP4A subfamily: Functional analysis by immunohistochemistry and in Situ hybridization". En Methods in Enzymology, 273–83. Elsevier, 1991. http://dx.doi.org/10.1016/0076-6879(91)06097-m.

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Actas de conferencias sobre el tema "CYP4A11"

Borin, Thaiz F., Sehar Ali, Kartik Angara, Mohammad Rashid, Stephanie Myers, Divya Chawla, Roxan Ara, Iryna Lebedyeva, Bhagelu R. Achyut y Ali S. Arbab. "Abstract 127: CYP4A11 overexpression increases aggressiveness in glioblastoma and breast cancer". En Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-127.

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Han, Mingzhi, Shuai Wang, Xingang Li, Jian Wang y Rolf Bjerkvig. "Abstract LB-295: Therapeutic implications of altered cholesterol homeostasis mediated by loss of CYP46A1 in human glioblastoma". En Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-lb-295.

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Kacher, Radhia, Vincent Kappes, Antonin Lamazière, Nicolas Heck, Gaëtan Despres, Luliia Dembitskaia, Elodie Perrin et al. "I13 Striatal regulation of cholesterol metabolism by CYP46A1 is associated with multiple benefits in huntington’s disease knock-in mice models". En EHDN 2018 Plenary Meeting, Vienna, Austria, Programme and Abstracts. BMJ Publishing Group Ltd, 2018. http://dx.doi.org/10.1136/jnnp-2018-ehdn.249.

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