Dissertation/ Thesis
Role of the phosphatase activity of soluble epoxide hydrolase in the regulation of metabolic and cardiovascular homeostasis ; Rôle de l'activité phosphatase de l'époxyde hydrolase soluble dans la régulation de l'homéostasie métabolique et cardiovasculaire.
| Τίτλος: | Role of the phosphatase activity of soluble epoxide hydrolase in the regulation of metabolic and cardiovascular homeostasis ; Rôle de l'activité phosphatase de l'époxyde hydrolase soluble dans la régulation de l'homéostasie métabolique et cardiovasculaire. |
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| Συγγραφείς: | Leuillier, Matthieu |
| Συνεισφορές: | Nouvelles Cibles Pharmacologiques de la Protection Endothéliale et de l'Insuffisance Cardiaque (EnVI), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université, Jérémy Bellien |
| Πηγή: | https://theses.hal.science/tel-04841981 ; Cardiologie et système cardiovasculaire. Normandie Université, 2019. Français. ⟨NNT : 2019NORMR150⟩. |
| Στοιχεία εκδότη: | CCSD |
| Έτος έκδοσης: | 2019 |
| Συλλογή: | Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| Θεματικοί όροι: | Cardiometabolic homeostasis, Cardiovascular homeostasis, Metabolic homeostasis, Soluble epoxide hydrolase, Homéostasie cardiométabolique, Homéostasie cardiovasculaire, Homéostasie métabolique, Epoxyde hydrolase soluble, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system |
| Περιγραφή: | Nearly 40 years after its initial discovery in 1972, soluble epoxide hydrolase (sEH), encoded by the EPHX2 gene, was shown in 2003 to be a bifunctional protein that exhibits not only an epoxide hydrolase activity on its C-terminal domain but also a lipid phosphatase activity on its N-terminal domain. Indeed, the hydrolase activity metabolizes epoxides of polyunsaturated fatty acids. In particular, sEH converts the vasodilator and anti-inflammatory epoxyeicosatrienoic acids converts, generated by cytochromes P450, into dihydroxyeicosatrienoic acids, which are less biologically active. This activity is now the target of a new class of pharmacologicla inhibitors. Unlike the biological function of the hydrolase activity, the biological function of sEH phosphatase activity remains, this time, unknown. Although shown originally to contribute to the stabilization of hydrolase activity or dimerization of the protein, some recent data indicate that the sEH phosphatase metabolizes also important lipid mediators, such as intracellular lysophosphatidic acids, involved in a wide range of biological functions such as vascular tone and inflammation, into monoacylglycerols. In addition, in vitro studies also suggested that the two activities of sEH have a complementary role in cholesterol regulation and vascular homeostasis. Although recombinant mice that do not express the EPHX2 gene have been around for some time, they do not allow to specifically study the phosphatase activity because both activities are eliminated. However, studies examining the differences between the effects of the genetic deletion of sEH and those of the pharmacological inhibition of its hydrolase activity indicate that the phosphatase activity of sEH probably has also a distinct physiological role. In our study, to assess the role of sEH phosphatase activity in absence of an inhibitor of this activity usable in vivo, original transgenic rats expressing sEH without phosphatase activity were generated using the CRISPR/Cas9 method. A thorough metabolic and ... |
| Τύπος εγγράφου: | doctoral or postdoctoral thesis |
| Γλώσσα: | French |
| Relation: | NNT: 2019NORMR150 |
| DOI: | 10.70675/5b0c2a46zee6az4508z9e51zb46f12261b45 |
| Διαθεσιμότητα: | https://theses.hal.science/tel-04841981 https://theses.hal.science/tel-04841981v1/document https://theses.hal.science/tel-04841981v1/file/matthieuleuillier.pdf https://doi.org/10.70675/5b0c2a46zee6az4508z9e51zb46f12261b45 |
| Rights: | https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Αριθμός Καταχώρησης: | edsbas.D9C40A17 |
| Βάση Δεδομένων: | BASE |
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