title: A novel peptide binding to the cytoplasmic domain of class A scavenger receptor reduces lipid uptake in THP-1 macrophages.
abstract: 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.
authors.affiliation: Institute of Reproductive Medicine, Key Laboratory of Human Functional Genomics, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yiming
authors.initials: Y
authors.lastname: Xu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ben
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Shen
authors.initials: S
authors.lastname: Yue
authors.forename: Hui
authors.initials: H
authors.lastname: Bai
authors.forename: Yaoyu
authors.initials: Y
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Leming
authors.initials: L
authors.lastname: Fan
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
mesh_terms: 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
chemical_list: D019151:Peptide Library; D010455:Peptides; D011993:Recombinant Fusion Proteins; D051117:Scavenger Receptors, Class A; D048056:Mitogen-Activated Protein Kinase 9