| RRC ID |
69762
|
| Author |
Tsuguto Masaki, Yoshio Kodera, Michishige Terasaki, Kazumi Fujimoto, Tsutomu Hirano, Masayoshi Shichiri
|
| Title |
GIP_HUMAN[22–51] is a new proatherogenic peptide identified by native plasma peptidomics
|
| Journal |
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.
|
| Volume |
11
|
| Published |
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
|
| Resource |
| Human and Animal Cells |
THP-1 |
