Cytoprotective effects of the flavonoid quercetin by activating mitochondrial BKCa channels in endothelial cells. - 18/09/21
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Abstract |
Mitochondrial potassium channels have been implicated in cytoprotective mechanisms. Activation of the mitochondrial large-conductance Ca2+-regulated potassium (mitoBKCa) channel is important for protecting brain tissue against stroke damage as well as heart tissue against ischemia damage. In this paper, we examine the effect of the natural flavonoid quercetin as an activator of the mitoBKCa channel. Quercetin has a beneficial effect on many processes in the human body and interacts with many receptors and signaling pathways. We found that quercetin acts on mitochondria as a mitoBKCa channel opener. The activation observed with the patch-clamp technique was potent and increased the channel open probability from approximately 0.35 to 0.95 at + 40 mV in the micromolar concentration range. Moreover, quercetin at a concentration of 10 µM protected cells by reducing damage from treatment factors (tumor necrosis factor α and cycloheximide) by 40%, enhancing cellular migration and depolarizing the mitochondrial membrane. Moreover, the presence of quercetin increased the gene expression and protein level of the mitoBKCa β3 regulatory subunit. The observed cytoprotective effects suggested the involvement of BKCa channel activation. Additionally, the newly discovered mitoBKCa activator quercetin elucidates a new mitochondrial pathway that is beneficial for vascular endothelial cells.
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Highlights |
• | Quercetin activates mitoBKCa at a concentration ten times lower than BKCa from the plasma membrane. |
• | Quercetin treatment is nontoxic to endothelial cells and protects from damage caused by TNF-α/cycloheximide. |
• | Protective effects of quercetin can be associated with activation of mitoBKCa channel. |
• | Quercetin accelerates the migration of endothelial cells and depolarizes the inner mitochondrial membrane. |
• | Presence of the quercetin regulates the gene expression and protein level of the mitoBKCa channel subunits. |
Keywords : Endothelium, Mitochondria, Mitochondrial potassium channels, Quercetin, Cytoprotection, Mitochondrial membrane potential, Apoptosis, Necrosis, Cell migration
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Vol 142
Article 112039- octobre 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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