Coenzyme Q10 Attenuates Platelet Thromboxane A2 Generation through Regulating the Protein Kinase A/Cytosolic Phospholipase A2 Signaling Pathway

被引:0
|
作者
Ya F. [1 ]
Zhang C. [2 ]
Chen B. [3 ]
Gu S. [1 ]
Jia X. [1 ]
机构
[1] Institute of Preventive Medicine, School of Public Health, Dali University, Dali
[2] Hekou Customs of the People's Republic of China, Hekou
[3] Department of Nutrition, Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning
来源
| 1600年 / Chinese Chamber of Commerce卷 / 42期
关键词
Cardiovascular diseases; Coenzyme Q[!sub]10[!/sub; Cytosolic phospholipase A[!sub]2[!/sub; Platelet; Thromboxane A[!sub]2[!/sub;
D O I
10.7506/spkx1002-6630-20200608-108
中图分类号
学科分类号
摘要
Objective: Thromboxane A2 (TxA2) derived from platelets can facilitate atherosclerosis and thrombosis. Previous studies have demonstrated that coenzyme Q10 (CoQ10) attenuates platelet activation, aggregation and thrombus formation. Our present study aimed to investigate the effect of CoQ10 on TxA2 generation and to clarify the underlying mechanisms. Methods: Gel-filtered platelets prepared from heathy adults were incubated with different concentrations of CoQ10 (0, 1, 10 and 100 μmol/L) for 50 min. After agonist activation, the level of TxB2 secreted from platelets was determined by enzymelinked immunosorbent assay. The phosphorylation of cytosolic phospholipase A2 (cPLA2) was measured by Western blot. Results: CoQ10 significantly inhibited platelet TxA2 generation induced by several agonists, including thrombin, collagen and convulxin. Western blot showed that CoQ10 significantly down-regulated thrombin- and collagen-induced cPLA2 phosphorylation. Moreover, pyrrophenone, a cPLA2 specific inhibitor, showed no any additive effects on TxA2 generation when combined with CoQ10. Furthermore, the inhibitory effect of CoQ10 on agonist-induced platelet cPLA2 phosphorylation and TxA2 generation was almost completely reversed by protein kinase A (PKA) inhibitor H89. Conclusion: CoQ10 can attenuate agonist-induced platelet TxA2 generation, and the mechanism is mainly through regulating the PKA/cPLA2 signaling pathway. © 2021, China Food Publishing Company. All right reserved.
引用
收藏
页码:130 / 136
页数:6
相关论文
共 27 条
  • [1] WENDELBOE A M, RASKOB G E., Global burden of thrombosis: epidemiologic aspects, Circulation Research, 118, 9, pp. 1340-1347, (2016)
  • [2] YEUNG J, LI W J, HOLINSTAT M., Platelet signaling and disease: targeted therapy for thrombosis and other related diseases, Pharmacological Reviews, 70, 3, pp. 526-548, (2018)
  • [3] EL HAOUARI M., Platelet oxidative stress and its relationship with cardiovascular diseases in type 2 diabetes mellitus patients, Current Medicinal Chemistry, 26, 22, pp. 4145-4165, (2019)
  • [4] THON J N, ITALIANO J E., Platelets: production, morphology and ultrastructure, Handbook of Experimental Pharmacology, 210, pp. 3-22, (2012)
  • [5] FRANCO A T, CORKEN A, WARE J., Platelets at the interface of thrombosis, inflammation, and cancer, Blood, 126, 5, pp. 582-588, (2015)
  • [6] LINDEMANN S, KRAMER B, SEIZER P, Et al., Platelets, inflammation and atherosclerosis, Journal of Thrombosis and Haemostasis, 5, pp. 203-211, (2007)
  • [7] FONTANA P, ZUFFEREY A, DAALI Y, Et al., Antiplatelet therapy: targeting the TxA<sub>2</sub> pathway, Journal of Cardiovascular Translational Research, 7, 1, pp. 29-38, (2014)
  • [8] YUHKI K, KASHIWAGI H, KOJIMA F, Et al., Roles of prostanoids in the pathogenesis of cardiovascular diseases, International Angiology, 29, pp. 19-27, (2010)
  • [9] PATRONO C, CIABATTONI G, DAVI G., Thromboxane biosynthesis in cardiovascular diseases, Stroke, 21, pp. IV130-IV133, (1990)
  • [10] NAIK M U, PATEL P, DERSTINE R, Et al., Ask1 regulates murine platelet granule secretion, thromboxane A<sub>2</sub> generation, and thrombus formation, Blood, 129, 9, pp. 1197-1209, (2017)