RRC ID 43593
著者 Kumano-Kuramochi M, Shimozu Y, Wakita C, Ohnishi-Kameyama M, Shibata T, Matsunaga S, Takano-Ishikawa Y, Watanabe J, Goto M, Xie Q, Komba S, Uchida K, Machida S.
タイトル Identification of 4-hydroxy-2-nonenal-histidine adducts that serve as ligands for human lectin-like oxidized LDL receptor-1.
ジャーナル Biochem J
Abstract LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) is an endothelial scavenger receptor that is important for the uptake of OxLDL (oxidized low-density lipoprotein) and contributes to the pathogenesis of atherosclerosis. However, the precise structural motifs of OxLDL that are recognized by LOX-1 are unknown. In the present study, we have identified products of lipid peroxidation of OxLDL that serve as ligands for LOX-1. We used CHO (Chinese-hamster ovary) cells that stably express LOX-1 to evaluate the ability of BSA modified by lipid peroxidation to compete with AcLDL (acetylated low-density lipoprotein). We found that HNE (4-hydroxy-2-nonenal)-modified proteins most potently inhibited the uptake of AcLDL. On the basis of the findings that HNE-modified BSA and oxidation of LDL resulted in the formation of HNE-histidine Michael adducts, we examined whether the HNE-histidine adducts could serve as ligands for LOX-1. The authentic HNE-histidine adduct inhibited the uptake of AcLDL in a dose-dependent manner. Furthermore, we found the interaction of LOX-1 with the HNE-histidine adduct to have a dissociation constant of 1.22×10(-8) M using a surface plasmon resonance assay. Finally, we showed that the HNE-histidine adduct stimulated the formation of reactive oxygen species and activated extracellular-signal-regulated kinase 1/2 and NF-κB (nuclear factor κB) in HAECs (human aortic endothelial cells); these signals initiate endothelial dysfunction and lead to atherosclerosis. The present study provides intriguing insights into the molecular details of LOX-1 recognition of OxLDL.
巻・号 442(1)
ページ 171-80
公開日 2012-2-15
DOI 10.1042/BJ20111029
PII BJ20111029
PMID 22077443
MeSH Aldehydes / metabolism* Aldehydes / pharmacology Animals Aorta / metabolism CHO Cells Cricetinae Endothelium, Vascular / cytology Histidine / analogs & derivatives* Histidine / metabolism Histidine / pharmacology Humans Ligands Lipoproteins, LDL / metabolism Reactive Oxygen Species / metabolism Scavenger Receptors, Class E / metabolism*
IF 4.097
引用数 25
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 CHO