About: Amiodarone impairs trafficking through late endosomes inducing a Niemann-Pick C-like phenotype

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About: Amiodarone impairs trafficking through late endosomes inducing a Niemann-Pick C-like phenotype Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Amiodarone impairs trafficking through late endosomes inducing a Niemann-Pick C-like phenotype
Creator	Baritussio, Aldo Calistri, Arianna Palù, Giorgio Salata, Cristiano Nadai, Matteo Bergonzini, Valeria Bigler, Laurent Dal Zoppo, Daniele Faggin, Elisabetta Orlando, Rocco Pettenazzo, Andrea Piccoli, Elena Ha, Riem Mucignat Caretta, Carla Vecchio, Claudia
source	Elsevier; Medline; PMC
abstract	Abstract Patients treated with amiodarone accumulate lysobisphosphatidic acid (LBPA), also known as bis(monoacylglycero)phosphate, in airway secretions and develop in different tissues vacuoles and inclusion bodies thought to originate from endosomes. To clarify the origin of these changes, we studied in vitro the effects of amiodarone on endosomal activities like transferrin recycling, Shiga toxin processing, ESCRT-dependent lentivirus budding, fluid phase endocytosis, proteolysis and exosome secretion. Furthermore, since the accumulation of LBPA might point to a broader disturbance in lipid homeostasis, we studied the effect of amiodarone on the distribution of LBPA, unesterified cholesterol, sphingomyelin and glycosphyngolipids. Amiodarone analogues were also studied, including the recently developed derivative dronedarone. We found that amiodarone does not affect early endosomal activities, like transferrin recycling, Shiga toxin processing and lentivirus budding. Amiodarone, instead, interferes with late compartments of the endocytic pathway, blocking the progression of fluid phase endocytosis and causing fusion of organelles, collapse of lumenal structures, accumulation of undegraded substrates and amassing of different types of lipids. Not all late endocytic compartments are affected, since exosome secretion is spared. These changes recall the Niemann-Pick type-C phenotype (NPC), but originate by a different mechanism, since, differently from NPC, they are not alleviated by cholesterol removal. Studies with analogues indicate that basic pKa and high water-solubility at acidic pH are crucial requirements for the interference with late endosomes/lysosomes and that, in this respect, dronedarone is at least as potent as amiodarone. These findings may have relevance in fields unrelated to rhythm control.
has issue date	2011-11-01(xsd:dateTime)
bibo:doi	10.1016/j.bcp.2011.07.090
bibo:pmid	21878321
has license	els-covid
sha1sum (hex)	be00868cd51f203546241a111dda2d5b75945e62
schema:url	https://doi.org/10.1016/j.bcp.2011.07.090
resource representing a document's title	Amiodarone impairs trafficking through late endosomes inducing a Niemann-Pick C-like phenotype
has PubMed Central identifier	PMC7092840
has PubMed identifier	21878321
schema:publication	Biochemical Pharmacology
resource representing a document's body	covid:be00868cd51f203546241a111dda2d5b75945e62#body_text
is schema:about of	named entity 'processing' named entity 'inclusion bodies' named entity 'organelles' named entity 'studied' named entity 'lysosomes' named entity 'lipid' named entity 'respect' named entity 'amiodarone' named entity 'transferrin' covid:arg/be00868cd51f203546241a111dda2d5b75945e62 named entity 'tissues' named entity 'amiodarone' named entity 'mechanism' named entity 'endocytic' named entity 'types' named entity 'clarify' named entity 'cholesterol' named entity 'homeostasis' named entity 'endocytic' named entity 'substrates' named entity 'NPC' named entity 'secretion' named entity 'derivative' named entity 'late' named entity 'interferes' named entity 'endocytic pathway' named entity 'vacuoles' named entity 'organelles' named entity 'acidic pH' named entity 'amiodarone' named entity 'amiodarone' named entity 'endosomal' named entity 'lumenal' named entity 'lipid' named entity 'ESCRT' named entity 'homeostasis' named entity 'pKa' named entity 'fluid phase' named entity 'endosomes' named entity 'transferrin' named entity 'inclusion bodies' named entity 'cholesterol' named entity 'Shiga toxin' named entity 'late endosomes' named entity 'phenotype' named entity 'PBS' named entity 'dextran' named entity '0.01' named entity 'vesicles' named entity 'phospholipids' named entity 'iodine' named entity 'lysosomes' named entity 'amiodarone' named entity 'SP-A' named entity 'early endosomes' named entity 'lipids' named entity 'amiodarone' named entity 'dronedarone' named entity 'water solubility' named entity 'Amiodarone' named entity 'tetramethylrhodamine' named entity 'endocytic pathway' named entity 'lysosomes' named entity 'phenotype' named entity 'lysosomes' named entity 'amiodarone' named entity 'endosomes'

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