Lysosomal acid lipase is the major acid retinyl ester hydrolase in cultured human hepatic stellate cells but not essential for retinyl ester degradation.
Hepatic stellate cell
Lipase
Liver
Retinol
Retinyl ester
Vitamin A
Journal
Biochimica et biophysica acta. Molecular and cell biology of lipids
ISSN: 1879-2618
Titre abrégé: Biochim Biophys Acta Mol Cell Biol Lipids
Pays: Netherlands
ID NLM: 101731727
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
10
10
2019
revised:
22
04
2020
accepted:
25
04
2020
pubmed:
4
5
2020
medline:
22
12
2020
entrez:
4
5
2020
Statut:
ppublish
Résumé
Vitamin A is stored as retinyl esters (REs) in lipid droplets of hepatic stellate cells (HSCs). To date, two different pathways are known to facilitate the breakdown of REs: (i) Hydrolysis of REs by neutral lipases, and (ii) whole lipid droplet degradation in autolysosomes by acid hydrolysis. In this study, we evaluated the contribution of neutral and acid RE hydrolases to the breakdown of REs in human HSCs. (R)-Bromoenol lactone (R-BEL), inhibitor of adipose triglyceride lipase (ATGL) and patatin-like phospholipase domain-containing 3 (PNPLA3), the hormone-sensitive lipase (HSL) inhibitor 76-0079, as well as the serine-hydrolase inhibitor Orlistat reduced neutral RE hydrolase activity of LX-2 cell-lysates between 20 and 50%. Interestingly, in pulse-chase experiments, R-BEL, 76-0079, as well as Orlistat exerted little to no effect on cellular RE breakdown of LX-2 cells as well as primary human HSCs. In contrast, Lalistat2, a specific lysosomal acid lipase (LAL) inhibitor, virtually blunted acid in vitro RE hydrolase activity of LX-2 cells. Accordingly, HSCs isolated from LAL-deficient mice showed RE accumulation and were virtually devoid of acidic RE hydrolase activity. In pulse-chase experiments however, LAL-deficient HSCs, similar to LX-2 cells and primary human HSCs, were not defective in degrading REs. In summary, results demonstrate that ATGL, PNPLA3, and HSL contribute to neutral RE hydrolysis of human HSCs. LAL is the major acid RE hydrolase in HSCs. Yet, LAL is not limiting for RE degradation under serum-starvation. Together, results suggest that RE breakdown of HSCs is facilitated by (a) so far unknown, non-Orlistat inhibitable RE-hydrolase(s).
Identifiants
pubmed: 32361002
pii: S1388-1981(20)30122-0
doi: 10.1016/j.bbalip.2020.158730
pmc: PMC7279957
mid: EMS86502
pii:
doi:
Substances chimiques
Carboxylic Ester Hydrolases
EC 3.1.1.-
retinyl esterase
EC 3.1.1.-
LIPA 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
158730Subventions
Organisme : Austrian Science Fund FWF
ID : F 7310
Pays : Austria
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 : W 901
Pays : Austria
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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