christian lacks lino cardenas

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  Article: Micromanaging microRNAs: using murine models to study microRNAs in lung fibrosis

  Christian L. Lino Cardenas, Naftali Kaminski, Daniel J. Kass
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  ABSTRACT: MicroRNAs are implicated in many biological and pathological processes and are emerging as key actors in lung health and disease. Specific patterns of dysre- gulated microRNAs have been found in idiopathic pulmonary fibrosis (IPF), an untreatable interstitial lung disease of unknown etiology. IPF is characterized by dramatic and extensive phenotypic changes in the lung that include alveolar cell hyperplasia, fibroblast proliferation and formation of myofibroblast foci, deposition of extracellular matrix, and changes in lung transcrip- tional programming. Here, we discuss the latest insights about the role of microRNAs in lung fibrosis with a focus on the contribution of animal models of disease to the derivation of these insights
  Drug Discovery Today Disease Models 01/2013;
• Article: Genetic polymorphism of CYP4A11 and CYP4A22 genes and in silico insights from comparative 3D modelling in a French population.

  Christian L Lino Cardenas, Nicolas Renault, Amaury Farce, Christelle Cauffiez, Delphine Allorge, Jean-Marc Lo-Guidice, Michel Lhermitte, Philippe Chavatte, Franck Broly, Dany Chevalier
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  ABSTRACT: The CYP4A subfamily is known to ω-hydroxylate the endogenous arachidonic acid into 20-hydroxyeicosatetranoic acid, which has renovascular and tubular functions. The aim of this work was to report a comprehensive investigation of the CYP4A11 and CYP4A22 genetic polymorphisms in a French population. Using PCR-SSCP and sequencing strategies, a total of 26 sequence variations were identified comprising 3 missense mutations for CYP4A11 (Ser404Phe, Phe434Ser and Arg505His) and 7 missense mutations for CYP4A22 (Arg126Trp, Gly130Ser, Asn152Tyr, Val185Phe, Cys231Arg, Leu428Pro and Leu509Phe). In comparison with SNPs reported in the database (dbSNP) of the National Center for Biotechnology information (NCBI), 6 and 3 novel polymorphisms were identified in CYP4A11 and CYP4A22, respectively. The potential impact of the amino acid substitutions on the structure and/or catalytic activity of the enzymes has been estimated by the construction and validation of the CYP4A 3D models. These results could be helpful for further investigations of the potential role of CYP4A variants in the genetic susceptibility to cardiovascular diseases in humans such as arterial hypertension.
  Gene 07/2011; 487(1):10-20. · 2.34 Impact Factor
• Article: Arachidonic acid ω-hydroxylase CYP4A11: inter-ethnic variations in the 8590T>C loss-of-function variant.

  Christian Lacks Lino Cardenas, Aurore Devos, Aminata Toure, Jaime Cardenas Garcia, Abderraouf Kenani, Florence Migot-Nabias, Franck Broly, Dany Chevalier
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  ABSTRACT: The human Cytochrome P450 4A11 (CYP4A11) is a major ω-hydroxylase involved in the regulation of blood pressure in the kidney through the conversion of arachidonic acid into 20-hydroxyeicosatetraenoic acid (20-HETE). Previous studies have reported a significant association between the 8590T>C genetic variant of CYP4A11 and hypertension. Interestingly, several population-based studies have reported ethnic differences in the prevalence of hypertension, with the highest prevalence in African populations. The aim of this work was to determine the frequency and inter-ethnic comparison of the CYP4A11 (8590T>C) functional polymorphism, in five new ethnic groups: European (99 French Caucasians), African (36 Gabonese and 50 Senegalese), South American (60 Peruvians) and North African (53 Tunisians) populations, using polymerase chain reaction-single strand conformational polymorphism and sequencing strategies. We confirmed that the CYP4A11 (8590T>C) functional polymorphism exhibits inter-ethnic frequency differences. Noteworthy, the highest 8590C allele frequency was observed in the Tunisian (30.2%), followed by Senegalese (20%) populations. In addition, the CC genotype was only found in the Gabonese and Tunisian populations (5.6% and 8.4%, respectively). These populations may be of major interest to help to clarify the linkage between hypertension and CYP4A11 (8590T>C) genotype in African populations. These findings provide data for further studies that investigate the potential association of CYP4A11 (8590T>C) variant with an incidence of hypertension genesis in respect of ethnicity.
  Molecular Biology Reports 05/2011; 39(2):1503-8. · 2.93 Impact Factor
• Article: Inter-ethnic variability of three functional polymorphisms affecting the IMPDH2 gene.

  Anne Garat, Christian Lacks Lino Cardenas, Arnaud Lionet, Aurore Devos, François Glowacki, Abderraouf Kenani, Florence Migot-Nabias, Delphine Allorge, Jean-Marc Lo-Guidice, Franck Broly, Christelle Cauffiez
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  ABSTRACT: Human type II inosine monophosphate dehydrogenase (IMPDH2) is a key enzyme in the purine nucleotide biosynthetic pathway and constitutes a pivotal biological target for immunosuppressant and antiviral drugs. Several Single Nucleotide Polymorphisms (SNP) affecting the IMPDH2 gene sequence have been reported with potential functional relevance and could impact drugs response. We aimed to determine the frequency of three of these polymorphisms, namely g.3375C>T (Leu(263)Phe), c.-95T>G and IVS7+10T>C, in Caucasians, Tunisians, Peruvians and Black Africans (Gabonese and Senegalese). The g.3375C>T and c.-95T>G polymorphisms are rare with a Minor Allele Frequency ≤1.0% in our populations, whereas the third variant, IVS7+10T>C, is more frequent and displays large interethnic variations, with an allelic frequency ranging from 14.6% in the French Caucasian population studied to less than 2% in Black African and Peruvian populations. This ethnic-related data might contribute to a better understanding of the variability in clinical outcome and/or dose adjustments of drugs that are IMPDH inhibitors such as mycophenolic acid.
  Molecular Biology Reports 12/2010; 38(8):5185-8. · 2.93 Impact Factor
• Article: Genetic polymorphisms of glycine N-acyltransferase (GLYAT) in a French Caucasian population.

  Christian Lacks Lino Cardenas, Joanna Bourgine, Christelle Cauffiez, Delphine Allorge, Jean Marc Lo-Guidice, Frank Broly, Dany Chevalier
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  ABSTRACT: In humans, the glycine N-acyltransferase enzyme (GLYAT) is thought to be important in the detoxification of endogenous and xenobiotic compounds which contain a carboxylic acid group, such as benzoic, isovaleric, or acetylsalicylic acids. The aim of this work was to report a comprehensive investigation of GLYAT genetic polymorphisms in DNA samples from 55 subjects of French Caucasian origin, using polymerase chain reaction-single-strand conformation polymorphism and sequencing strategies. Seven different polymorphisms of the GLYAT gene were identified, including two polymorphisms in the 5' flanking region of the gene (g.-8457C>T and g.-8010A>G), two polymorphisms in intron 5 (g.13931A>G and g.13944C>T) and three missense mutations in exon 2 (g.49T>A; p.Ser17Thr), exon 5 (g.13886A>G; p.Asn156Ser) and exon 6 (g.14435C>T; p.Arg199Cys). In addition to the wild-type allele GLYAT*1 (2.7%), four novel alleles were identified: GLYAT*2A (75.5%), *2B (4.5%), *3 (16.4%) and *4 (0.9%), and five different genotypes. Localisation of the p.Ser17Thr and p.Arg199Cys missense mutations in predicted secondary structures suggest that these variants might have a potential role on the GLYAT protein activity. These results could be helpful in investigating the potential association of GLYAT variants with an incidence of reduced efficiency in xenobiotic carboxylic acids detoxification in humans.
  Xenobiotica 10/2010; 40(12):853-61. · 1.79 Impact Factor