KIAA1363 affects retinyl ester turnover in cultured murine and human hepatic stellate cells.
JW480
KIAA1363
hepatic stellate cells
liver
retinol
retinyl ester hydrolase
vitamin A
Journal
Journal of lipid research
ISSN: 1539-7262
Titre abrégé: J Lipid Res
Pays: United States
ID NLM: 0376606
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
08
10
2021
revised:
14
12
2021
accepted:
19
01
2022
pubmed:
2
2
2022
medline:
27
4
2022
entrez:
1
2
2022
Statut:
ppublish
Résumé
Large quantities of vitamin A are stored as retinyl esters (REs) in specialized liver cells, the hepatic stellate cells (HSCs). To date, the enzymes controlling RE degradation in HSCs are poorly understood. In this study, we identified KIAA1363 (also annotated as arylacetamide deacetylase 1 or neutral cholesterol ester hydrolase 1) as a novel RE hydrolase. We show that KIAA1363 is expressed in the liver, mainly in HSCs, and exhibits RE hydrolase activity at neutral pH. Accordingly, addition of the KIAA1363-specific inhibitor JW480 largely reduced RE hydrolase activity in lysates of cultured murine and human HSCs. Furthermore, cell fractionation experiments and confocal microscopy studies showed that KIAA1363 localizes to the endoplasmic reticulum. We demonstrate that overexpression of KIAA1363 in cells led to lower cellular RE content after a retinol loading period. Conversely, pharmacological inhibition or shRNA-mediated silencing of KIAA1363 expression in cultured murine and human HSCs attenuated RE degradation. Together, our data suggest that KIAA1363 affects vitamin A metabolism of HSCs by hydrolyzing REs at the endoplasmic reticulum, thereby counteracting retinol esterification and RE storage in lipid droplets.
Identifiants
pubmed: 35101424
pii: S0022-2275(22)00006-2
doi: 10.1016/j.jlr.2022.100173
pmc: PMC8953624
pii:
doi:
Substances chimiques
Retinyl Esters
0
Vitamin A
11103-57-4
Hydrolases
EC 3.-
Carboxylic Ester Hydrolases
EC 3.1.1.-
Nceh1 protein, mouse
EC 3.1.1.-
NCEH1 protein, human
EC 3.1.1.13
Sterol Esterase
EC 3.1.1.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100173Subventions
Organisme : Austrian Science Fund FWF
ID : I 3535
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : P 31638
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : P 34899
Pays : Austria
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
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