The Use of Triphenyl Phosphonium Cation Enhances the Mitochondrial Antiplatelet Effect of the Compound Magnolol
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, howev...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/16/2/210 |
| _version_ | 1797618811649654784 |
|---|---|
| author | Francisca Tellería Santiago Mansilla Diego Méndez Magdalena Sepúlveda Ramiro Araya-Maturana Laura Castro Andrés Trostchansky Eduardo Fuentes |
| author_facet | Francisca Tellería Santiago Mansilla Diego Méndez Magdalena Sepúlveda Ramiro Araya-Maturana Laura Castro Andrés Trostchansky Eduardo Fuentes |
| author_sort | Francisca Tellería |
| collection | DOAJ |
| description | 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<sub>50</sub>. 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. |
| first_indexed | 2024-03-11T08:17:50Z |
| format | Article |
| id | doaj.art-5d2c727e03d94c37b3958964edd70bfb |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T08:17:50Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-5d2c727e03d94c37b3958964edd70bfb2023-11-16T22:36:31ZengMDPI AGPharmaceuticals1424-82472023-01-0116221010.3390/ph16020210The Use of Triphenyl Phosphonium Cation Enhances the Mitochondrial Antiplatelet Effect of the Compound MagnololFrancisca Tellería0Santiago Mansilla1Diego Méndez2Magdalena Sepúlveda3Ramiro Araya-Maturana4Laura Castro5Andrés Trostchansky6Eduardo Fuentes7MIBI: 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, ChileDepartamento de Métodos Cuantitativos and Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo 11800, UruguayMIBI: 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, ChileMIBI: 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, ChileMIBI: Interdisciplinary Group on Mitochondrial Targeting and Bioenergetics, Instituto de Química de Recursos Naturales, Universidad de Talca, Talca 3460000, ChileDepartamento de Bioquímica and Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo 11800, UruguayDepartamento de Bioquímica and Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo 11800, UruguayMIBI: 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, ChileAlthough 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<sub>50</sub>. 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.https://www.mdpi.com/1424-8247/16/2/210plateletmitochondriamagnololtriphenylphosphoniumrespiration |
| spellingShingle | Francisca Tellería Santiago Mansilla Diego Méndez Magdalena Sepúlveda Ramiro Araya-Maturana Laura Castro Andrés Trostchansky Eduardo Fuentes The Use of Triphenyl Phosphonium Cation Enhances the Mitochondrial Antiplatelet Effect of the Compound Magnolol Pharmaceuticals platelet mitochondria magnolol triphenylphosphonium respiration |
| title | The Use of Triphenyl Phosphonium Cation Enhances the Mitochondrial Antiplatelet Effect of the Compound Magnolol |
| title_full | The Use of Triphenyl Phosphonium Cation Enhances the Mitochondrial Antiplatelet Effect of the Compound Magnolol |
| title_fullStr | The Use of Triphenyl Phosphonium Cation Enhances the Mitochondrial Antiplatelet Effect of the Compound Magnolol |
| title_full_unstemmed | The Use of Triphenyl Phosphonium Cation Enhances the Mitochondrial Antiplatelet Effect of the Compound Magnolol |
| title_short | The Use of Triphenyl Phosphonium Cation Enhances the Mitochondrial Antiplatelet Effect of the Compound Magnolol |
| title_sort | use of triphenyl phosphonium cation enhances the mitochondrial antiplatelet effect of the compound magnolol |
| topic | platelet mitochondria magnolol triphenylphosphonium respiration |
| url | https://www.mdpi.com/1424-8247/16/2/210 |
| work_keys_str_mv | AT franciscatelleria theuseoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT santiagomansilla theuseoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT diegomendez theuseoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT magdalenasepulveda theuseoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT ramiroarayamaturana theuseoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT lauracastro theuseoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT andrestrostchansky theuseoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT eduardofuentes theuseoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT franciscatelleria useoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT santiagomansilla useoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT diegomendez useoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT magdalenasepulveda useoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT ramiroarayamaturana useoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT lauracastro useoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT andrestrostchansky useoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol AT eduardofuentes useoftriphenylphosphoniumcationenhancesthemitochondrialantiplateleteffectofthecompoundmagnolol |