RRC ID 39046
著者 Taniguchi M, Ochiai A, Matsushima K, Tajima K, Kato T, Saitoh E, Tanaka T.
タイトル Endotoxin-neutralizing activity and mechanism of action of a cationic α-helical antimicrobial octadecapeptide derived from α-amylase of rice.
ジャーナル Peptides
Abstract We have previously reported that AmyI-1-18, an octadecapeptide derived from α-amylase (AmyI-1) of rice, is a novel cationic α-helical peptide that exhibited antimicrobial activity against human pathogens, including Porphyromonas gingivalis, Pseudomonas aeruginosa, Propionibacterium acnes, Streptococcus mutans, and Candida albicans. In this study, to further investigate the potential functions of AmyI-1-18, we examined its inhibitory ability against the endotoxic activities of lipopolysaccharides (LPSs, smooth and Rc types) and lipid A from Escherichia coli. AmyI-1-18 inhibited the production of endotoxin-induced nitric oxide (NO), an inflammatory mediator, in mouse macrophages (RAW264) in a concentration-dependent manner. The results of a chromogenic Limulus amebocyte lysate assay illustrated that the ability [50% effective concentration (EC50): 0.17 μM] of AmyI-1-18 to neutralize lipid A was similar to its ability (EC50: 0.26 μM) to neutralize LPS, suggesting that AmyI-1-18 specifically binds to the lipid A moiety of LPS. Surface plasmon resonance analysis of the interaction between AmyI-1-18 and LPS or lipid A also suggested that AmyI-1-18 directly binds to the lipid A moiety of LPS because the dissociation constant (KD) of AmyI-1-18 with lipid A is 5.6×10(-10) M, which is similar to that (4.3×10(-10) M) of AmyI-1-18 with LPS. In addition, AmyI-1-18 could block the binding of LPS-binding protein to LPS, although its ability was less than that of polymyxin B. These results suggest that AmyI-1-18 expressing antimicrobial and endotoxin-neutralizing activities is useful as a safe and potent host defense peptide against pathogenic Gram-negative bacteria in many fields of healthcare.
巻・号 75
ページ 101-8
公開日 2016-1-1
DOI 10.1016/j.peptides.2015.11.006
PII S0196-9781(15)30006-1
PMID 26643956
MeSH Animals Anti-Inflammatory Agents / pharmacology* Antimicrobial Cationic Peptides / chemistry* Antimicrobial Cationic Peptides / pharmacology Drug Evaluation, Preclinical Inhibitory Concentration 50 Lipid A / chemistry* Lipid A / pharmacology Mice Nitric Oxide / biosynthesis Oryza / enzymology Peptide Fragments / chemistry* Peptide Fragments / pharmacology Plant Proteins / chemistry* RAW 264.7 Cells alpha-Amylases / chemistry*
IF 2.843
引用数 10
WOS 分野 PHARMACOLOGY & PHARMACY ENDOCRINOLOGY & METABOLISM BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)