1. Kinetics of plasma apolipoprotein E isoforms by LC-MS/MS: a pilot study
- Author
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Blanchard, Valentin, Ramin-Mangata, Stéphane, Billon-Crossouard, Stephanie, Aguesse, Audrey, Durand, Manon, Chemello, Kevin, Nativel, Brice, Flet, Laurent, Chetiveaux, Maud, Jacobi, David, Bard, Jean-Marie, Ouguerram, Khadija, Lambert, Gilles, Krempf, Michel, Croyal, Mikael, Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine Ouest (CRNH Ouest), Université de Nantes (UN), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Pharmacie, Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), FR 3473 Institut universitaire Mer et Littoral (IUML), Université de Bretagne Sud (UBS)-Le Mans Université (UM)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Nantes (UN)-École Centrale de Nantes (ECN), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre de recherche en nutrition humaine Ouest, Nutrition périnatale [Nantes] (Centres de Recherche en Nutrition Humaine - CRNH), Centre de Recherche en Nutrition Humaine - Ouest, INRA: UMR1280 Physiologie des adaptations (UMR1280), Institut National de la Recherche Agronomique (INRA), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS), Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), UMR 1280 Physiologie des Adaptations Nutritionnelles, and Institut de Cancérologie de l'Ouest
- Subjects
Male ,Apolipoprotein E2 ,[SDV]Life Sciences [q-bio] ,Apolipoprotein E4 ,Apolipoprotein E3 ,Médecine humaine et pathologie ,lipoprotein/metabolism ,Pilot Projects ,QD415-436 ,apolipoprotein E isoforms ,Biochemistry ,Lipoproteins/Kinetics ,tandem mass spectrometry ,Humans ,Protein Isoforms ,Food and Nutrition ,liquid chromatography ,lipoprotein/kinetics ,Chromatography, High Pressure Liquid ,peptide ,stable isotope tracers ,Middle Aged ,Kinetics ,Lipoproteins/Metabolism ,Alimentation et Nutrition ,Human health and pathology ,lipids (amino acids, peptides, and proteins) ,Patient-Oriented and Epidemiological Research - Abstract
International audience; Human apolipoprotein E (apoE) exhibits three major isoforms (apoE2, apoE3, and apoE4) corresponding to polymorphism in theAPOEgene. Total plasma apoE concentrations are closely related to these isoforms but the underlying mechanisms are unknown. We aimed to describe the kinetics of apoE individual isoforms to explore the mechanisms for variable total apoE plasma concentrations. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to discriminate between isoforms by identifying specific peptide sequences in subjects (3 E2/E3, 3 E3/E3 and 3 E3/E4 phenotypes) who received a primed constant infusion of2H3-leucine for 14 hours. ApoE concentrations and leucine enrichments were measured hourly in plasma. Concentrations of apoE2 were higher than apoE3, and concentrations of apoE4 were lower than apoE3. There was no difference between apoE3 and apoE4 catabolic rates and between apoE2 and apoE3 production rates, but apoE2 catabolic rates and apoE4 production rates were lower. Then, the mechanisms leading to the difference in total plasma apoE concentrations are related to contrasted kinetics of the isoforms. Production or catabolic rates are differently affected according to the specific isoforms. From these grounds, studies on the regulation of the involved biochemical pathways and the impact of pathological environments are now warranted.
- Published
- 2018