1. Bis(monoacylglycero)phosphate, a new lipid signature of endosome-derived extracellular vesicles
- Author
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Audrey Jalabert, Audrey Villard-Garon, Sophie Rome, Annette Draeger, Pascal Colosetti, Christophe O. Soulage, Françoise Hullin-Matsuda, Isabelle Delton, Cyrille Bergerot, Céline Luquain-Costaz, Elisabeth Errazuriz-Cerda, Valentin Leuzy, Mathilde Di Filippo, Annie Durand, Baptiste Fourmaux, Maxence Rabia, René Köffel, Philippe Moulin, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie intégrative, cellulaire et moléculaire (PICM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM), and French Ministery of education Institut National de la Sante et de la Recherche Medicale (Inserm) University of Bern SFD (Societe Francophone du Diabete_AE 2016) VML (Vaincre les Maladies Lysosomales_convention AO2018-6)
- Subjects
Male ,0301 basic medicine ,THP-1 Cells ,Endosome ,[SDV]Life Sciences [q-bio] ,Phospholipid ,Amiodarone ,Pilot Projects ,Endosomes ,Exosomes ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Lysosomal storage diseases ,medicine ,Extracellular ,Animals ,Humans ,610 Medicine & health ,Aged ,Phospholipidosis ,Kidney ,030102 biochemistry & molecular biology ,CD63 ,Chemistry ,Macrophages ,Bis(monoacylglycero)phosphate ,General Medicine ,Middle Aged ,Extracellular vesicles ,Lysobisphosphatidic acid ,Endolysosome ,Microvesicles ,Rats ,Cell biology ,Docosahexaenoic acid ,HEK293 Cells ,030104 developmental biology ,medicine.anatomical_structure ,interest ,Monoglycerides ,Female ,Kidney Diseases ,Lysophospholipids ,Lysosomes ,Anti-Arrhythmia Agents ,Biomarkers - Abstract
International audience; Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid (LBPA), is a phospholipid specifically enriched in the late endosome-lysosome compartment playing a crucial role for the fate of endocytosed components. Due to its presence in extracellular fluids during diseases associated with endolysosomal dysfunction, it is considered as a possible biomarker of disorders such as genetic lysosomal storage diseases and cationic amphiphilic drug-induced phospholipidosis. However, there is no true validation of this biomarker in human studies, nor a clear identification of the carrier of this endolysosome-specific lipid in biofluids. The present study demonstrates that in absence of any sign of renal failure, BMP, especially all docosahexaenoyl containing species, are significantly increased in the urine of patients treated with the antiarrhythmic drug amiodarone. Such urinary BMP increase could reflect a generalized drug-induced perturbation of the endolysosome compartment as observed in vitro with amiodarone-treated human macrophages. Noteworthy, BMP was associated with extracellular vesicles (EVs) isolated from human urines and extracellular medium of human embryonic kidney HEK293 cells and co-localizing with classical EV protein markers CD63 and ALIX. In the context of drug-induced endolysosomal dysfunction, increased BMP-rich EV release could be useful to remove excess of undigested material. This first human pilot study not only reveals BMP as a urinary biomarker of amiodarone-induced endolysosomal dysfunction, but also highlights its utility to prove the endosomal origin of EVs, also named as exosomes. This peculiar lipid already known as a canonical late endosome-lysosome marker, may be thus considered as a new lipid marker of urinary exosomes.
- Published
- 2020