PMID- 32867213 OWN - NLM STAT- MEDLINE DCOM- 20210222 LR - 20210222 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 17 DP - 2020 Aug 27 TI - Mitoquinone (MitoQ) Inhibits Platelet Activation Steps by Reducing ROS Levels. LID - 10.3390/ijms21176192 [doi] LID - 6192 AB - Platelet activation plays a key role in cardiovascular diseases. The generation of mitochondrial reactive oxygen species (ROS) has been described as a critical step required for platelet activation. For this reason, it is necessary to find new molecules with antiplatelet activity and identify their mechanisms of action. Mitoquinone (MitoQ) is a mitochondria-targeted antioxidant that reduces mitochondrial overproduction of ROS. In this work, the antiplatelet effect of MitoQ through platelet adhesion and spreading, secretion, and aggregation was evaluated. Thus MitoQ, in a non-toxic effect, decreased platelet adhesion and spreading on collagen surface, and expression of P-selectin and CD63, and inhibited platelet aggregation induced by collagen, convulxin, thrombin receptor activator peptide-6 (TRAP-6), and phorbol 12-myristate 13-acetate (PMA). As an antiplatelet mechanism, we showed that MitoQ produced mitochondrial depolarization and decreased ATP secretion. Additionally, in platelets stimulated with antimycin A and collagen MitoQ significantly decreased ROS production. Our findings showed, for the first time, an antiplatelet effect of MitoQ that is probably associated with its mitochondrial antioxidant effect. FAU - Mendez, Diego AU - Mendez D AUID- ORCID: 0000-0003-0156-2913 AD - Thrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Universidad de Talca, Talca 3460000, Chile. FAU - Arauna, Diego AU - Arauna D AUID- ORCID: 0000-0001-7132-991X AD - Thrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Universidad de Talca, Talca 3460000, Chile. FAU - Fuentes, Francisco AU - Fuentes F AD - Escuela de Medicina, Universidad de Talca, Talca 3460000, Chile. FAU - Araya-Maturana, Ramiro AU - Araya-Maturana R AUID- ORCID: 0000-0002-5082-9146 AD - Instituto de Quimica de Recursos Naturales, Universidad de Talca, Talca 3460000, Chile. FAU - Palomo, Ivan AU - Palomo I AD - Thrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Universidad de Talca, Talca 3460000, Chile. FAU - Alarcon, Marcelo AU - Alarcon M AUID- ORCID: 0000-0001-7596-5382 AD - Thrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Universidad de Talca, Talca 3460000, Chile. FAU - Sebastian, David AU - Sebastian D AUID- ORCID: 0000-0002-7260-3869 AD - Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08007 Barcelona, Spain. AD - Departament de Bioquimica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, 08007 Barcelona, Spain. AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain. FAU - Zorzano, Antonio AU - Zorzano A AD - Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08007 Barcelona, Spain. AD - Departament de Bioquimica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, 08007 Barcelona, Spain. AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain. FAU - Fuentes, Eduardo AU - Fuentes E AUID- ORCID: 0000-0003-0099-4108 AD - Thrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Universidad de Talca, Talca 3460000, Chile. LA - eng PT - Journal Article DEP - 20200827 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antioxidants) RN - 0 (CD63 protein, human) RN - 0 (Oligopeptides) RN - 0 (Organophosphorus Compounds) RN - 0 (P-Selectin) RN - 0 (Phorbol Esters) RN - 0 (Reactive Oxygen Species) RN - 0 (Ser-Phe-Phe-Leu-Arg-Asn) RN - 0 (Tetraspanin 30) RN - 1339-63-5 (Ubiquinone) RN - 20839-06-9 (phorbol-12-myristate) RN - 47BYS17IY0 (mitoquinone) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - 9007-34-5 (Collagen) SB - IM MH - Adenosine Triphosphate/metabolism MH - Animals MH - Antioxidants/*pharmacology MH - Blood Platelets/drug effects/*metabolism MH - Cells, Cultured MH - Collagen/metabolism MH - Humans MH - Mice MH - Mitochondria/metabolism MH - Oligopeptides/pharmacology MH - Organophosphorus Compounds/*pharmacology MH - P-Selectin/metabolism MH - Phorbol Esters/pharmacology MH - Platelet Activation/drug effects MH - Reactive Oxygen Species/*metabolism MH - Tetraspanin 30/metabolism MH - Ubiquinone/*analogs & derivatives/pharmacology PMC - PMC7503844 OTO - NOTNLM OT - MitoQ OT - ROS OT - mitochondria OT - mitoquinone OT - platelets COIS- The authors declare no conflict of interest. EDAT- 2020/09/02 06:00 MHDA- 2021/02/23 06:00 PMCR- 2020/09/01 CRDT- 2020/09/02 06:00 PHST- 2020/06/30 00:00 [received] PHST- 2020/08/18 00:00 [revised] PHST- 2020/08/19 00:00 [accepted] PHST- 2020/09/02 06:00 [entrez] PHST- 2020/09/02 06:00 [pubmed] PHST- 2021/02/23 06:00 [medline] PHST- 2020/09/01 00:00 [pmc-release] AID - ijms21176192 [pii] AID - ijms-21-06192 [pii] AID - 10.3390/ijms21176192 [doi] PST - epublish SO - Int J Mol Sci. 2020 Aug 27;21(17):6192. doi: 10.3390/ijms21176192.