論文 - 詳細
| RRC ID | 69762 |
|---|---|
| 著者 | Tsuguto Masaki, Yoshio Kodera, Michishige Terasaki, Kazumi Fujimoto, Tsutomu Hirano, Masayoshi Shichiri |
| タイトル | GIP_HUMAN[22–51] is a new proatherogenic peptide identified by native plasma peptidomics |
| ジャーナル | Scientific Reports |
| Abstract |
We recently established a new plasma peptidomic technique and comprehensively identified a large number of low-molecular weight and low-abundance native peptides using a single drop of human plasma. To discover a novel polypeptide that potently modulates the cardiovascular system, we performed a bioinformatics analysis of the large-scale identification results, sequentially synthesized the selected peptide sequences, tested their biological activities, and identified a 30-amino-acid proatherogenic peptide, GIP_HUMAN[22–51], as a potent proatherosclerotic peptide hormone. GIP_HUMAN[22–51] has a common precursor with the glucose-dependent insulinotropic polypeptide (GIP) and is located immediately N-terminal to GIP. Chronic infusion of GIP_HUMAN[22–51] into ApoE−/− mice accelerated the development of aortic atherosclerotic lesions, which were inhibited by co-infusions with an anti-GIP_HUMAN[22–51] antibody. GIP_HUMAN[22–51] increased the serum concentrations of many inflammatory and proatherogenic proteins,
whereas neutralising antibodies reduced their levels. GIP_HUMAN[22–51] induced IκB-α degradation and nuclear translocation of NF-κB in human vascular endothelial cells and macrophages. Immunoreactive GIP_HUMAN[22–51] was detected in human tissues but there was no colocalization with the GIP. The plasma GIP_HUMAN[22–51] concentration in healthy humans determined using a stable-isotope tagged peptide was approximately 0.6 nM. This study discovered a novel endogenous proatherogenic peptide by using a human plasma native peptidomic resource. |
| 巻・号 | 11 |
| 公開日 | 2021-12-1 |
| DOI | 10.1038/s41598-021-93862-w |
| PMID | 34262109 |
| PMC | PMC8280211 |
| MeSH | Animals Atherosclerosis / chemically induced Atherosclerosis / pathology Biomarkers / blood Calcium / metabolism Cells, Cultured Computer Simulation Gastric Inhibitory Polypeptide / blood Gastric Inhibitory Polypeptide / chemistry* Humans Mass Spectrometry Mice, Knockout, ApoE NF-kappa B / metabolism Peptide Fragments / chemistry Peptide Fragments / pharmacology Peptides / blood* Peptides / pharmacology* Peptides / toxicity |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1 |