Kampa 2019 ASMRM2019

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Kampa RP, Sęk A, Kicińska A, Jarmuszkiewicz W, Szewczyk A, Bednarczyk P (2019) Natural compounds as a modulators of mitochondrial large conductance Ca2+-regulated potassium channel (mitoBKCa) activity. ASMRM2019.

Link: ASMRM 2019

Kampa RP, Sek A, Kicinska A, Jarmuszkiewicz W, Szewczyk A, Bednarczyk P (2019)

Event: Asia Society for Mitochondrial Research and Medicine

Flavonoids belong to a large group of polyphenolic compounds that are widely present in plants. Certain flavonoids, including luteolin, quercetin or cyanidin, have been shown to be cardioprotective. Although the antioxidant effect of flavonoids has been long thought to be a crucial factor accounting for cellular cardioprotection. Also, mitochondrial pathways (including mitochondrial large-conductance Ca2+-regulated (mitoBKCa) channel) are presently emerging potential targets for a specific pharmacological action of flavonoids in the anti-ischemic strategies.

The aim of these studies is the characterization of interactions between cardioprotective flavonoids and the mitoBKCa channel present in the inner mitochondrial membrane of the endothelial cells.

Single channel activity of the mitoBKCa was measured with patch-clamp of the mitoplasts isolated from endothelial cells (EA.hy926). Application of 3 μM cyanidin has an inhibitory effect. In the presence of luteolin, changes of open probability of the mitoBKCa channel were not observed. Furthermore, regulation of the mitoBKCa channel by flavonoids were studied in the presence of 0.5 mM dithiothreitol. Changes in the redox state causes that luteolin and cyanidin have activatory properties. Open probability of the mitoBKCa channel increase from 0.02 to 0.36 at -40 mV in the presence 10 uM cyanidin. However, quercetin has strong activating properties both under control conditions and reduced by DTT. In addition, it was found that the quercetin-activated channel at various concentrations is not inhibited by the main inhibitor for this channel, paxilline. Possible cytoprotective properties of flavonoids with using apoptosis/necrosis assays were also studied.

We expect that our studies describing the regulation of mitochondrial potassium channels by the natural substances of plant origin will bring us closer to a better understanding of flavonoid-induced cytoprotective mechanisms.


Bioblast editor: Plangger M O2k-Network Lab: PL Poznan Jarmuszkiewicz W, PL Warsaw Szewczyk A, PL Warsaw Bednarczyk P


Labels: MiParea: mt-Membrane, Pharmacology;toxicology 


Tissue;cell: Endothelial;epithelial;mesothelial cell 

Enzyme: Inner mt-membrane transporter  Regulation: Ion;substrate transport 



Flavonoids 

Affiliations and support

Kampa RP(1,2), Sęk A(2,3), Kicińska A(4), Jarmuszkiewicz W(4), Szewczyk A(2), Bednarczyk P(1)
  1. Dept Biophysics, Warsaw Univ Life Sciences (SGGW)
  2. Lab Intracellular Ion Channels, Nencki Inst Experimental Biology
  3. Fac Chemistry, Univ Warsaw; Warsaw
  4. Lab Bioenergetics, Adam Mickiewicz Univ, Poznan; Poland
This study was supported by a grant 2016/21/B/NZ1/02769 from the National Science Centre, Poland. Work implemented as a part of Operational Project Knowledge Education Development 2014-2020 cofinanced by European Social Fund (to Aleksandra Sęk).