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Evaluation de la fonction de NOX1 sur modèle animal transgènique

Abstract : The NOX family enzyme is constituted by Superoxide-generating NADPH oxidases homologues of gp91Phox; as the well characterized NOX2 (new denomination for gp91Phox) their catalytic subunit exhibits a common structure of 6 or 7 transmemmbrane domaine (ROS). The total number of enzymes in the family increased to 7 throught the past 5 years ; it includes, NOX1, NOX2, NOX3, NOX4, NOX5 et DUOX 1 et DUOX2 ; Tissue and cellular distributions of mRNA expression of the enzymes are well defined and show that superoxide generating enzyme are quasi-ubiquitous. General functions are Reactive oxygen species (ROS) dependent but their cellular localisations are of importance. NOX2 produces ROS in stimulated phagocytes and is the known microbicidal enzyme. NOX3 is responsible for vestibular dysfunction and DUOX1 and DUOX 2 allow iodination to thyroglobuline resulting in biosynthesis of thyroid hormon. While mRNA expressions of the other NOXs (namely NOX1, NOX4 and NOX5) are well defined, their biological functions are still not known. In vitro and ex vivo data provide only indirect informations which not allow understanding complexes interplay of the biological function.
We have then generated NOX1-deficient mice to further investigate directly the in vivo functions of NOX1 in colon and vascular tissues.
First, we used a F3 generation mice to determine whether NOX1 participate in the antibacterial defences and whether it limits bacterial translocation. We show that NOX1 is involved in the severity of Dextran Sulfate Sodium induced colitis via bacterial colonic flora and decrease the bacterial translocation in the gut. However, we have to be cautious because of the weakness of homology of the genetic background (87.5%) which in turn, may modify the results.
Second, we investigated whether NOX1 regulates basal blood pressure and participates in angiotensin II induced hypertension. All experiments were realized with F6 generation mice. NOX1-deficient mice had lower basal blood pressure, an almost complete loss of sustained blood pressure response to angiotensin II and were strongly protected from ATII-induced aortic dissection. Our results establish an important role for NOX1 in the vascular ATII response, in particular extracellular matrix accumulation, regulation of gene expression, and cross talk with the nitric oxide system.
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Contributor : Gaetan Gavazzi <>
Submitted on : Thursday, May 10, 2007 - 4:32:15 PM
Last modification on : Friday, November 6, 2020 - 4:09:58 AM
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Gaetan Gavazzi. Evaluation de la fonction de NOX1 sur modèle animal transgènique. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2006. Français. ⟨tel-00145555⟩

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