Gly[14]-humanin inhibits ox-LDL uptake and stimulates cholesterol efflux in macrophage-derived foam cells.
Foam cell formation, which is caused by imbalanced cholesterol influx and efflux by macrophages, plays a vital role in the occurrence and development of atherosclerosis. Humanin (HN), a mitochondria-derived peptide, can prevent the production of reactive oxygen species and death of human aortic endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL) and has a protective effect on patients with in early atherosclerosis. However, the effects of HN on the regulation of cholesterol metabolism in RAW 264.7 macrophages are still unknown. This study was designed to investigate the role of [Gly14]-humanin (HNG) in lipid uptake and cholesterol efflux in RAW 264.7 macrophages. Flow cytometry and live cell imaging results showed that HNG reduced Dil-ox-LDL accumulation in the RAW 264.7 macrophages. A similar result was obtained for lipid accumulation by measuring cellular cholesterol content. Western blot analysis showed that ox-LDL treatment upregulated not only the protein expression of CD36 and LOX-1, which mediate ox-LDL endocytosis, but also ATP-binding cassette (ABC) transporter A1 and ABCG1, which mediate ox-LDL exflux. HNG pretreatment inhibited the upregulation of CD36 and LOX-1 levels, prompting the upregulation of ABCA1 and ABCG1 levels induced by ox-LDL. Therefore we concluded that HNG could inhibit ox-LDL-induced macrophage-derived foam cell formation, which occurs because of a decrease in lipid uptake and an increase in cholesterol efflux from macrophage cells.
Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Wa-Wa
WW
Zhu
Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Shu-Rong
SR
Wang
Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Zhi-Hua
ZH
Liu
Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Yong-Jun
YJ
Cao
Institute of Neuroscience, Soochow University, Suzhou 215123, China.
Fen
F
Wang
Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Jing
J
Wang
Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Institute of Neuroscience, Soochow University, Suzhou 215123, China.
Chun-Feng
CF
Liu
Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China. Electronic address: 13013883877@126.com.
Ying
Y
Xie
Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Ying
Y
Xie
Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China. Electronic address: Zhangyanlin0012006@163.com.
Yan-Lin
YL
Zhang
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism*; D005487:Foam Cells / Q000166:cytology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics*; D051379:Mice; D000067996:RAW 264.7 Cells
D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; C427211:humanin; C099252:oxidized low density lipoprotein; D002784:Cholesterol
ABCA1; ABCG1; Cluster of differentiation 36; HNG; Lectin-like ox-LDL receptor-1; Macrophage cells