Inhibitory effects of ethyl pyruvate on platelet aggregation and phosphatidylserine exposure.
作者： Wenjin Li , Xinyu Yang , Minyuan Peng , Can Li , Guangfu Mu
DOI: 10.1016/J.BBRC.2017.04.087
关键词: Pharmacology 、 Mechanism of action 、 Protein kinase C 、 Thrombin 、 Chemistry 、 Platelet activation 、 Protein kinase B 、 Biochemistry 、 Platelet 、 Lactate dehydrogenase 、 Agonist
摘要: Ethyl pyruvate (EP) is a stable lipophilic derivative. Studies demonstrated that EP shows potent anti-oxidation, anti-inflammatory and anti-coagulant effects. Inflammation coagulation are closely interacted with platelet activation. However, it unclear whether has anti-platelet Therefore, we investigated the effect of in this study in vitro. We found inhibited agonists induced platelets aggregation, ATP release adhesion to collagen. Flow cytometric analysis revealed agonist PAC-1 binding, as well P-selectin CD40L expression. The underlying mechanism action may involve inhibition PI3K/Akt Protein Kinase C (PKC) signaling pathways. Additionally, dose dependently PS exposure by high concentration thrombin. Lactate dehydrogenase (LDH) activity assay mice count implied have no toxic on platelets. first report attenuates in vitro, suggesting inhibitory effects also play important roles improvement inflammation disorder related animal models.
sci-hub.se 参考文章(30)
WeiHong Dong, Bolin Cai, Geber Peña, Vadim Pisarenko, Gergely Vida, Danielle Doucet, Marlon Lee, Susan Sharpe, Qi Lu, Da-Zhong Xu, Laura Ramos, Edwin A. Deitch, Luis Ulloa, Ethyl pyruvate prevents inflammatory responses and organ damage during resuscitation in porcine hemorrhage. Shock. ,vol. 34, pp. 205- 213 ,(2010) , 10.1097/SHK.0B013E3181CC0C63
M. T. HARPER, A. W. POOLE, Diverse functions of protein kinase C isoforms in platelet activation and thrombus formation Journal of Thrombosis and Haemostasis. ,vol. 8, pp. 454- 462 ,(2010) , 10.1111/J.1538-7836.2009.03722.X
J. W. M. HEEMSKERK, N. J. A. MATTHEIJ, J. M. E. M. COSEMANS, Platelet‐based coagulation: different populations, different functions Journal of Thrombosis and Haemostasis. ,vol. 11, pp. 2- 16 ,(2013) , 10.1111/JTH.12045
Paola E. J. van der Meijden, Simone M. Schoenwaelder, Marion A. H. Feijge, Judith M. E. M. Cosemans, Imke C. A. Munnix, Reinhard Wetzker, Regine Heller, Shaun P. Jackson, Johan W. M. Heemskerk, Dual P2Y12 receptor signaling in thrombin‐stimulated platelets – involvement of phosphoinositide 3‐kinase β but not γ isoform in Ca2+ mobilization and procoagulant activity FEBS Journal. ,vol. 275, pp. 371- 385 ,(2008) , 10.1111/J.1742-4658.2007.06207.X
IF Guarda, CJ Correia, AC Breithaupt-Faloppa, SG Ferreira, AC Moreno, MB Martinez, M Rocha-e-Silva, P Sannomiya, Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment Clinics. ,vol. 70, pp. 508- 514 ,(2015) , 10.6061/CLINICS/2015(07)08
Jecko Thachil, Platelets in Inflammatory Disorders: A Pathophysiological and Clinical Perspective. Seminars in Thrombosis and Hemostasis. ,vol. 41, pp. 572- 581 ,(2015) , 10.1055/S-0035-1556589
M. T. HARPER, A. W. POOLE, PKC inhibition markedly enhances Ca2+ signaling and phosphatidylserine exposure downstream of protease‐activated receptor‐1 but not protease‐activated receptor‐4 in human platelets Journal of Thrombosis and Haemostasis. ,vol. 9, pp. 1599- 1607 ,(2011) , 10.1111/J.1538-7836.2011.04393.X
L. Ulloa, M. Ochani, H. Yang, M. Tanovic, D. Halperin, R. Yang, C. J. Czura, M. P. Fink, K. J. Tracey, Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation Proceedings of the National Academy of Sciences of the United States of America. ,vol. 99, pp. 12351- 12356 ,(2002) , 10.1073/PNAS.192222999
Seung-Woo Kim, Ji-Young Jeong, Hyun Ji Kim, Ji-Seon Seo, Pyung-Lim Han, Sung-Hwa Yoon, Ja-Kyeong Lee, Combination Treatment with Ethyl Pyruvate and Aspirin Enhances Neuroprotection in the Postischemic Brain Neurotoxicity Research. ,vol. 17, pp. 39- 49 ,(2010) , 10.1007/S12640-009-9075-4
Prabhakara Nagareddy, Susan S. Smyth, Inflammation and thrombosis in cardiovascular disease. Current Opinion in Hematology. ,vol. 20, pp. 457- 463 ,(2013) , 10.1097/MOH.0B013E328364219D