Tellería Francisca, Mansilla Santiago, Méndez Diego, Sepúlveda Magdalena, Araya-Maturana Ramiro, Castro Laura, Trostchansky Andrés, Fuentes Eduardo
MIBI: Interdisciplinary Group on Mitochondrial Targeting and Bioenergetics, Department of Clinical Biochemistry and Immunohematology, Thrombosis Research Center, Medical Technology School, Faculty of Health Sciences, Universidad de Talca, Talca 3480094, Chile.
Departamento de Métodos Cuantitativos and Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay.
Pharmaceuticals (Basel). 2023 Jan 30;16(2):210. doi: 10.3390/ph16020210.
Although platelets are anucleated cells, they have fully functional mitochondria, and currently, it is known that several processes that occur in the platelet require the action of mitochondria. There are plenty of mitochondrial-targeted compounds described in the literature related to cancer, however, only a small number of studies have approached their interaction with platelet mitochondria and/or their effects on platelet activity. Recent studies have shown that magnolia extract and mitochondria-targeted magnolol can inhibit mitochondrial respiration and cell proliferation in melanoma and oral cancer cells, respectively, and they can also induce ROS and mitophagy. In this study, the effect of triphenylphosphonium cation, linked by alkyl chains of different lengths, to the organic compound magnolol on human-washed platelets was evaluated. We demonstrated that the addition of triphenylphosphonium by a four-carbon linker to magnolol (MGN4) considerably enhanced the Magnolol antiplatelet effect by a 3-fold decrease in the IC. Additionally, platelets exposed to MGN4 5 µM showed several differences from the control including increased basal respiration, collagen-induced respiration, ATP-independent respiration, and reduced ATP-dependent respiration and non-mitochondrial respiration.
尽管血小板是无核细胞，但它们具有功能完备的线粒体，目前已知血小板中发生的几个过程都需要线粒体发挥作用。文献中有大量与癌症相关的线粒体靶向化合物，但只有少数研究探讨了它们与血小板线粒体的相互作用和/或对血小板活性的影响。最近的研究表明，木兰提取物和线粒体靶向的厚朴酚分别可以抑制黑色素瘤和口腔癌细胞中的线粒体呼吸和细胞增殖，它们还可以诱导活性氧（ROS）和线粒体自噬。在本研究中，评估了通过不同长度烷基链连接到有机化合物厚朴酚上的三苯基膦阳离子对人洗涤血小板的影响。我们证明，通过四碳连接子将三苯基膦添加到厚朴酚（MGN4）中，可使厚朴酚的抗血小板作用显著增强，IC降低了3倍。此外，暴露于5 µM MGN4的血小板与对照组相比表现出一些差异，包括基础呼吸增加、胶原诱导的呼吸增加、非ATP依赖性呼吸增加，以及ATP依赖性呼吸和非线粒体呼吸减少。
