Regulation of the Mitochondrial BK<sub>Ca</sub> Channel by the Citrus Flavonoid Naringenin as a Potential Means of Preventing Cell Damage
Naringenin, a flavanone obtained from citrus fruits and present in many traditional Chinese herbal medicines, has been shown to have various beneficial effects on cells both in vitro and in vivo. Although the antioxidant activity of naringenin has long been believed to be crucial for its effects on...
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MDPI AG
2020-06-01
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| author | Anna Kicinska Rafał P. Kampa Jan Daniluk Aleksandra Sek Wieslawa Jarmuszkiewicz Adam Szewczyk Piotr Bednarczyk |
| author_facet | Anna Kicinska Rafał P. Kampa Jan Daniluk Aleksandra Sek Wieslawa Jarmuszkiewicz Adam Szewczyk Piotr Bednarczyk |
| author_sort | Anna Kicinska |
| collection | DOAJ |
| description | Naringenin, a flavanone obtained from citrus fruits and present in many traditional Chinese herbal medicines, has been shown to have various beneficial effects on cells both in vitro and in vivo. Although the antioxidant activity of naringenin has long been believed to be crucial for its effects on cells, mitochondrial pathways (including mitochondrial ion channels) are emerging as potential targets for the specific pharmacological action of naringenin in cardioprotective strategies. In the present study, we describe interactions between the mitochondrial large-conductance calcium-regulated potassium channel (mitoBK<sub>Ca</sub> channel) and naringenin. Using the patch-clamp method, we showed that 10 µM naringenin activated the mitoBK<sub>Ca</sub> channel present in endothelial cells. In the presence of 30 µM Ca<sup>2+</sup>, the increase in the mitoBK<sub>Ca</sub> channel probability of opening from approximately 0.25 to 0.50 at −40 mV was observed. In addition, regulation of the mitoBK<sub>Ca</sub> channel by naringenin was dependent on the concentration of calcium ions. To confirm our data, physiological studies on the mitochondria were performed. An increase in oxygen consumption and a decrease in membrane potential was observed after naringenin treatment. In addition, contributions of the mitoBK<sub>Ca</sub> channel to apoptosis and necrosis were investigated. Naringenin protected cells against damage induced by tumor necrosis factor α (TNF-α) in combination with cycloheximide. In this study, we demonstrated that the flavonoid naringenin can activate the mitoBK<sub>Ca</sub> channel present in the inner mitochondrial membrane of endothelial cells. Our studies describing the regulation of the mitoBK<sub>Ca</sub> channel by this natural, plant-derived substance may help to elucidate flavonoid-induced cytoprotective mechanisms. |
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| last_indexed | 2024-03-10T18:46:46Z |
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| series | Molecules |
| spelling | doaj.art-bd5633569fa74de290165127ffac89d72023-11-20T05:29:57ZengMDPI AGMolecules1420-30492020-06-012513301010.3390/molecules25133010Regulation of the Mitochondrial BK<sub>Ca</sub> Channel by the Citrus Flavonoid Naringenin as a Potential Means of Preventing Cell DamageAnna Kicinska0Rafał P. Kampa1Jan Daniluk2Aleksandra Sek3Wieslawa Jarmuszkiewicz4Adam Szewczyk5Piotr Bednarczyk6Department of Bioenergetics, Adam Mickiewicz University, 61-614 Poznan, PolandDepartment of Physics and Biophysics, Institute of Biology, Warsaw University of Life Sciences—SGGW, 02-776 Warsaw, PolandLaboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, 02-093 Warsaw, PolandLaboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, 02-093 Warsaw, PolandDepartment of Bioenergetics, Adam Mickiewicz University, 61-614 Poznan, PolandLaboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, 02-093 Warsaw, PolandDepartment of Physics and Biophysics, Institute of Biology, Warsaw University of Life Sciences—SGGW, 02-776 Warsaw, PolandNaringenin, a flavanone obtained from citrus fruits and present in many traditional Chinese herbal medicines, has been shown to have various beneficial effects on cells both in vitro and in vivo. Although the antioxidant activity of naringenin has long been believed to be crucial for its effects on cells, mitochondrial pathways (including mitochondrial ion channels) are emerging as potential targets for the specific pharmacological action of naringenin in cardioprotective strategies. In the present study, we describe interactions between the mitochondrial large-conductance calcium-regulated potassium channel (mitoBK<sub>Ca</sub> channel) and naringenin. Using the patch-clamp method, we showed that 10 µM naringenin activated the mitoBK<sub>Ca</sub> channel present in endothelial cells. In the presence of 30 µM Ca<sup>2+</sup>, the increase in the mitoBK<sub>Ca</sub> channel probability of opening from approximately 0.25 to 0.50 at −40 mV was observed. In addition, regulation of the mitoBK<sub>Ca</sub> channel by naringenin was dependent on the concentration of calcium ions. To confirm our data, physiological studies on the mitochondria were performed. An increase in oxygen consumption and a decrease in membrane potential was observed after naringenin treatment. In addition, contributions of the mitoBK<sub>Ca</sub> channel to apoptosis and necrosis were investigated. Naringenin protected cells against damage induced by tumor necrosis factor α (TNF-α) in combination with cycloheximide. In this study, we demonstrated that the flavonoid naringenin can activate the mitoBK<sub>Ca</sub> channel present in the inner mitochondrial membrane of endothelial cells. Our studies describing the regulation of the mitoBK<sub>Ca</sub> channel by this natural, plant-derived substance may help to elucidate flavonoid-induced cytoprotective mechanisms.https://www.mdpi.com/1420-3049/25/13/3010endotheliummitochondriapotassium channelsnaringeninapoptosis/necrosis |
| spellingShingle | Anna Kicinska Rafał P. Kampa Jan Daniluk Aleksandra Sek Wieslawa Jarmuszkiewicz Adam Szewczyk Piotr Bednarczyk Regulation of the Mitochondrial BK<sub>Ca</sub> Channel by the Citrus Flavonoid Naringenin as a Potential Means of Preventing Cell Damage Molecules endothelium mitochondria potassium channels naringenin apoptosis/necrosis |
| title | Regulation of the Mitochondrial BK<sub>Ca</sub> Channel by the Citrus Flavonoid Naringenin as a Potential Means of Preventing Cell Damage |
| title_full | Regulation of the Mitochondrial BK<sub>Ca</sub> Channel by the Citrus Flavonoid Naringenin as a Potential Means of Preventing Cell Damage |
| title_fullStr | Regulation of the Mitochondrial BK<sub>Ca</sub> Channel by the Citrus Flavonoid Naringenin as a Potential Means of Preventing Cell Damage |
| title_full_unstemmed | Regulation of the Mitochondrial BK<sub>Ca</sub> Channel by the Citrus Flavonoid Naringenin as a Potential Means of Preventing Cell Damage |
| title_short | Regulation of the Mitochondrial BK<sub>Ca</sub> Channel by the Citrus Flavonoid Naringenin as a Potential Means of Preventing Cell Damage |
| title_sort | regulation of the mitochondrial bk sub ca sub channel by the citrus flavonoid naringenin as a potential means of preventing cell damage |
| topic | endothelium mitochondria potassium channels naringenin apoptosis/necrosis |
| url | https://www.mdpi.com/1420-3049/25/13/3010 |
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