Deubiquitination of CD36 by UCHL1 promotes foam cell formation.

Abstract

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.

• Authors: Xiaohong Xia, Qiong Xu, Mingke Liu, Xuke Chen, Xiaolin Liu, Jinchan He, Tumei Hu, Cuifu Yu, Hongbiao Huang, Shiming Liu, Ningning Liu
• Journal: Cell death & disease (Cell Death Dis) Vol. 11 Issue 8 Pg. 636 (08 15 2020) ISSN: 2041-4889 [Electronic] England
• PMID: 32801299 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter 1
• ATP-Binding Cassette Transporters
• CD36 Antigens
• Lipids
• Lipoproteins, LDL
• Scavenger Receptors, Class A
• oxidized low density lipoprotein
• Cholesterol
• Deubiquitinating Enzymes
• Ubiquitin Thiolesterase

Topics

• 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, metabolism)
• Ubiquitination