Oxidized low-density lipoprotein-binding specificity of the Asp-hemolysin-related synthetic peptides from Aspergillus fumigatus.
Oxidatively modified low-density lipoprotein (OxLDL) is present in atherosclerotic lesions and has been proposed to play an important role in atherogenesis. In the present study, in order to clarify the structure-binding activity relationship of Asp-hemolysin-related peptides to OxLDL, we investigated the interaction between Asp-hemolysin-related peptides consisting of 4 to 29 amino acid residues and OxLDL. The incubation of OxLDL with each Asp-hemolysin-related peptide resulted in the formation of an Asp-hemolysin/OxLDL complex. In particular, the tetrapeptide, YKDG (P-4), bound to OxLDL and inhibited the OxLDL-induced macrophage proliferation in a dose-dependent manner. Furthermore, we demonstrated that lysophosphatidylcholine (LysoPC) extracted from OxLDL inhibited the binding of P-21 to OxLDL in a dose-dependent manner and synthetic [14C]LysoPC bound to P-21. We propose here that the YKDG region is one of the important sites for the binding of these peptides to OxLDL, and LysoPC as a typical lipid moiety of OxLDL is attributed to the binding of OxLDL to these peptides.
Kumagai
Takeshi
T
Department of Environmental Health Science, Tohoku Pharmaceutical University, Miyagi, Japan. ta-kuma@tohoku-pharm.ac.jp
Tsutsumi
Hiromu
H
Ogawa
Norihiro
N
Naito
Saori
S
Ebina
Keiichi
K
Yokota
Katsushi
K
Nagata
Kiyoshi
K
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002250:Carbon Radioisotopes; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005656:Fungal Proteins / Q000138:chemical synthesis / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000138:chemical synthesis / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D011863:Radioimmunoassay; D013329:Structure-Activity Relationship
C089497:Asp-HS protein, Aspergillus fumigatus; D002250:Carbon Radioisotopes; D005656:Fungal Proteins; D006460:Hemolysin Proteins; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; C099252:oxidized low density lipoprotein