PMID- 32662128 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210621 IS - 1745-4514 (Electronic) IS - 0145-8884 (Linking) VI - 44 IP - 9 DP - 2020 Sep TI - A novel di-peptide Met-Glu from collagen hydrolysates inhibits platelet aggregation and thrombus formation via regulation of Gq-mediated signaling. PG - e13352 LID - 10.1111/jfbc.13352 [doi] AB - Increasing evidence has shown that collagen peptides had various biological activities. In this study, a novel antiplatelet peptide Met-Glu (ME) was separated and identified from silver carp skin by YMC ODS-A C18 separation and ESI-MS/MS analysis. Peptide ME inhibited platelet aggregation and secretion of platelet granules induced by ADP, thrombin and collagen, and significantly attenuated ferric chloride-induced thrombus formation in rats. It did not prolong the bleeding time in mice even at the dose of 300 mumol/kg body weight that showed potent anti-thrombosis effects. Additionally, peptide ME targeted at Gq-protein to downregulate the phosphorylation of PLCbeta, an important upstream effector of PI3K/Akt and Erk/MAPK signaling to inhibit intracellular calcium ion mobilization. These results suggest that peptide ME inhibited thrombosis in vivo and inhibited Gq-mediated signaling in platelets, indicating the possibility that ME could potentially be developed as a novel therapeutic agent in the prevention and treatment of thrombotic diseases. PRACTICAL APPLICATIONS: Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide. The proximal cause of CVDs is intravascular thrombosis formation, which mostly results from platelet activation, aggregation, and granules secretion. Traditional drugs in the prevention of thrombotic disease, such as aspirin and clopidogrel, are still limited for their side effects, especially bleeding complications. Collagen is a natural source for bioactive peptides and our previous study has shown that collagen peptides could inhibit platelet aggregation in vitro. Understanding the mechanism of collagen peptides on regulation of platelet activation and their in vivo anti-thrombosis activities were important for the development of novel-specific medical food in the prevention of thrombotic diseases. CI - (c) 2020 Wiley Periodicals LLC. FAU - Yang, Yijie AU - Yang Y AD - College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China. FAU - Song, Hongdong AU - Song H AD - College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China. FAU - Wang, Bo AU - Wang B AD - College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China. FAU - Tian, Qi AU - Tian Q AD - College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China. FAU - Li, Bo AU - Li B AUID- ORCID: 0000-0003-2726-2900 AD - College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China. AD - Key Laboratory of Functional Dairy, Ministry of Education, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200713 PL - United States TA - J Food Biochem JT - Journal of food biochemistry JID - 7706045 RN - 0 (Dipeptides) RN - 0 (Peptides) RN - 0 (Platelet Aggregation Inhibitors) RN - 0 (methionylglutamic acid) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Collagen MH - Dipeptides MH - Mice MH - Peptides/pharmacology MH - Phosphatidylinositol 3-Kinases MH - *Platelet Aggregation MH - Platelet Aggregation Inhibitors/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Tandem Mass Spectrometry MH - *Thrombosis/drug therapy/prevention & control OTO - NOTNLM OT - Gq signaling OT - anti-thrombosis OT - antiplatelet OT - collagen peptide EDAT- 2020/07/15 06:00 MHDA- 2021/06/22 06:00 CRDT- 2020/07/15 06:00 PHST- 2020/03/31 00:00 [received] PHST- 2020/05/13 00:00 [revised] PHST- 2020/05/31 00:00 [accepted] PHST- 2020/07/15 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/07/15 06:00 [entrez] AID - 10.1111/jfbc.13352 [doi] PST - ppublish SO - J Food Biochem. 2020 Sep;44(9):e13352. doi: 10.1111/jfbc.13352. Epub 2020 Jul 13.