Deubiquitination of CD36 by UCHL1 promotes foam cell formation.
ATP Binding Cassette Transporter 1
/ metabolism
ATP-Binding Cassette Transporters
/ genetics
Animals
Atherosclerosis
/ pathology
Biological Transport
CD36 Antigens
/ metabolism
Cell Line
Cholesterol
/ metabolism
Deubiquitinating Enzymes
/ metabolism
Foam Cells
/ metabolism
Humans
Lipid Metabolism
/ physiology
Lipids
Lipoproteins, LDL
/ metabolism
Macrophages
/ metabolism
Male
Mice
Mice, Inbred C57BL
Scavenger Receptors, Class A
/ metabolism
Ubiquitin Thiolesterase
/ genetics
Ubiquitination
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
15 08 2020
15 08 2020
Historique:
received:
12
05
2020
accepted:
04
08
2020
revised:
03
08
2020
entrez:
18
8
2020
pubmed:
18
8
2020
medline:
13
4
2021
Statut:
epublish
Résumé
Atherosclerosis-associated cardiovascular diseases are main causes leading to high mortality worldwide. Macrophage-derived foam cell formation via uptaking modified lipoproteins is the initial and core step in the process of atherosclerosis. Meanwhile, scavenger receptor is indispensable for the formation of foam cells. UCHL1, a deubiquitinase, has been widely studied in multiple cancers. UCHL1 could be an oncogene or a tumor suppressor in dependent of tumor types. It remains unknown whether UCHL1 influences cellular oxLDL uptake. Herein we show that UCHL1 deletion significantly inhibits lipid accumulation and foam cell formation. Subsequently, we found that UCHL1 inhibitor or siRNA downregulates the expression of CD36 protein whereas SR-A, ABCA1, ABCG1, Lox-1, and SR-B1 have no significant change. Furthermore, the treatment of UCHL1 inhibition increases the abundance of K48-polyubiquitin on CD36 and the suppression of lipid uptake induced by UCHL1 deficiency is attenuated by blocking CD36 activation. Our study concluded that UCHL1 deletion decreases foam cell formation by promoting the degradation of CD36 protein, indicating UCHL1 may be a potential target for atherosclerosis treatment.
Identifiants
pubmed: 32801299
doi: 10.1038/s41419-020-02888-x
pii: 10.1038/s41419-020-02888-x
pmc: PMC7429868
doi:
Substances chimiques
ATP Binding Cassette Transporter 1
0
ATP-Binding Cassette Transporters
0
CD36 Antigens
0
Lipids
0
Lipoproteins, LDL
0
Scavenger Receptors, Class A
0
oxidized low density lipoprotein
0
Cholesterol
97C5T2UQ7J
Deubiquitinating Enzymes
EC 3.4.19.12
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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