Regulation of the Mitochondrial BKCa Channel by the Citrus Flavonoid Naringenin as a Potential Means of Preventing Cell Damage

Molecules

Wieslawa Jarmuszkiewicz¹  Anna Kicinska¹  RafałP. Kampa²  Piotr Bednarczyk²  Adam Szewczyk³  Aleksandra Sek³  Jan Daniluk³ 

[1] Department of Bioenergetics, Adam Mickiewicz University, 61-614 Poznan, Poland;Department of Physics and Biophysics, Institute of Biology, Warsaw University of Life Sciences—SGGW, 02-776 Warsaw, Poland;Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland;

关键词: endothelium;    mitochondria;    potassium channels;    naringenin;    apoptosis/necrosis;   

DOI  :  10.3390/molecules25133010

来源: DOAJ

【 摘 要 】

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_Ca channel) and naringenin. Using the patch-clamp method, we showed that 10 µM naringenin activated the mitoBK_Ca channel present in endothelial cells. In the presence of 30 µM Ca²⁺, the increase in the mitoBK_Ca channel probability of opening from approximately 0.25 to 0.50 at -40 mV was observed. In addition, regulation of the mitoBK_Ca 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_Ca channel to apoptosis and necrosis were investigated. Naringenin protected cells against damage induced by tumor necrosis factor a (TNF-a) in combination with cycloheximide. In this study, we demonstrated that the flavonoid naringenin can activate the mitoBK_Ca channel present in the inner mitochondrial membrane of endothelial cells. Our studies describing the regulation of the mitoBK_Ca channel by this natural, plant-derived substance may help to elucidate flavonoid-induced cytoprotective mechanisms.

【 授权许可】

Unknown