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Bis(monoacylglycero)phosphate, a new lipid signature of endosome-derived extracellular vesicles
- Source :
- Biochimie, Biochimie, 2020, ⟨10.1016/j.biochi.2020.07.005⟩
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
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.
- 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
Subjects
Details
- ISSN :
- 03009084
- Volume :
- 178
- Database :
- OpenAIRE
- Journal :
- Biochimie
- Accession number :
- edsair.doi.dedup.....15d9635ec3b56ac0b8edbba60e968406