A novel peptide binding to the cytoplasmic domain of class A scavenger receptor reduces lipid uptake in THP-1 macrophages.
Class A scavenger receptor (SR-A) contributes primarily to lipid accumulation in cells. The cytoplasmic domain of SR-A (CSR-A) is responsible for internalization of the receptor-ligand complex into cells. In the present study we tried to reduce cellular uptake of acetylated low density lipoprotein (AcLDL) by inducing the interaction between the CSR-A and a novel peptide H11, which was screened from a phage-displayed peptide library. When H11 was fused with a cross membrane peptide TAT, the fusion peptide could enter cell efficiently. The peptide H11 inhibited the binding and uptake of DiI-AcLDL and attenuated lipid accumulation in the differentiated human acute monocytic leukemia cell line (THP-1) macrophages. Furthermore, the interaction of peptide H11 with the CSR-A inhibited the expression of SR-A protein as well as the phosphorylation of c-jun N-terminal kinase 2 (JNK2) in cells, which mediates cellular lipid accumulation-related signaling pathways. These results suggest that the CSR-A can be a potential target to prevent lipid accumulation in cells. The peptide H11 may be useful in regulating SR-A functions in macrophages.
Wang
Xiaohua
X
Institute of Reproductive Medicine, Key Laboratory of Human Functional Genomics, Nanjing Medical University, Nanjing 210029, People's Republic of China.
Zheng
Yuan
Y
Xu
Yiming
Y
Ben
Jingjing
J
Gao
Song
S
Zhu
Xudong
X
Zhuang
Yan
Y
Yue
Shen
S
Bai
Hui
H
Chen
Yaoyu
Y
Jiang
Li
L
Ji
Yong
Y
Xu
Yong
Y
Fan
Leming
L
Sha
Jiahao
J
He
Zhigang
Z
Chen
Qi
Q
D002460:Cell Line; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000037:antagonists & inhibitors; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D051117:Scavenger Receptors, Class A / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D019151:Peptide Library; D010455:Peptides; D011993:Recombinant Fusion Proteins; D051117:Scavenger Receptors, Class A; D048056:Mitogen-Activated Protein Kinase 9