Lysosome-associated membrane protein-2 deficiency increases the risk of reactive oxygen species-induced ferroptosis in retinal pigment epithelial cells.
AMD
Degeneration
Ferroptosis
Macula
ROS
Retinal pigment epithelium
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
08 01 2020
08 01 2020
Historique:
received:
12
10
2019
accepted:
18
10
2019
pubmed:
2
11
2019
medline:
28
7
2020
entrez:
2
11
2019
Statut:
ppublish
Résumé
Lysosome-associated membrane protein-2 (LAMP2), is a highly glycosylated lysosomal membrane protein involved in chaperone mediated autophagy. Mutations of LAMP2 cause the classic triad of myopathy, cardiomyopathy and encephalopathy of Danon disease (DD). Additionally, retinopathy has also been observed in young DD patients, leading to vision loss. Emerging evidence show LAMP2-deficiency to be involved in oxidative stress (ROS) but the mechanism remains obscure. In the present study, we found that tert-butyl hydroperoxide or antimycin A induced more cell death in LAMP2 knockdown (LAMP2-KD) than in control ARPE-19 cells. Mechanistically, LAMP2-KD reduced the concentration of cytosolic cysteine, resulting in low glutathione (GSH), inferior antioxidant capability and mitochondrial lipid peroxidation. ROS induced RPE cell death through ferroptosis. Inhibition of glutathione peroxidase 4 (GPx4) increased lethality in LAMP2-KD cells compared to controls. Cysteine and glutamine supplementation restored GSH and prevented ROS-induced cell death of LAMP2-KD RPE cells.
Identifiants
pubmed: 31672277
pii: S0006-291X(19)32046-7
doi: 10.1016/j.bbrc.2019.10.138
pmc: PMC6935401
mid: NIHMS1542272
pii:
doi:
Substances chimiques
LAMP2 protein, human
0
Lysosomal-Associated Membrane Protein 2
0
Reactive Oxygen Species
0
Glutamine
0RH81L854J
Glutathione
GAN16C9B8O
Cysteine
K848JZ4886
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
414-419Subventions
Organisme : NEI NIH HHS
ID : P30 EY003790
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY014104
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY025362
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY023079
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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