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The Impact of DIDS-Induced Inhibition of Voltage-Dependent Anion Channels (VDAC) on Cellular Response of Lymphoblastoid Cells to Ionizing Radiation

[ Vol. 13 , Issue. 5 ]

Author(s):

Magdalena Skonieczna, Artur Cieslar-Pobuda, Yuriy Saenko, Marek Foksinski, Ryszard Olinski, Joanna Rzeszowska-Wolny and Emilia Wiechec*   Pages 477 - 483 ( 7 )

Abstract:


Background: The voltage-dependent anion channels (VDAC) play an essential role in the cross talk between mitochondria and the rest of the cell. Their implication in cell life and cell death has been studied extensively in recent years. In this work we studied the impact of mitochondrial membrane (VDACs) on cell survival and response to X-ionizing radiation (IR) of human lymphoblastoid K562 cells.

Methods: The inhibition of VDACs was achieved by 4,4`-diisothiocyanostilbene-2,2`-disulfonic acid (DIDS) inhibitor and in vitro experiments including clonogenity assay, UV-visible spectrophotometry, comet assay and FACS analysis were implemented.

Results: Inhibition of VDAC led to augmentation of IR-induced apoptosis and ROS production. Additionally, DIDS affected repair of IR-induced DNA strand breaks and was in line with both induction of apoptosis and caspase activity. The IR-induced NO production was potently reduced by inhibition of VDAC.

Conclusion: Our results suggest that VDAC control cellular response to ionizing radiation through modulation of the ROS- and NO-dependent signaling pathways. Inhibition of VDAC with DIDS induced apoptosis in irradiated K562 lymphoblastoid cells points at DIDS, as a promising agent to enhance the effectiveness of radiotherapy.

Keywords:

4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS), voltage-dependent anion channel (VDAC), reactive oxygen species (ROS), ionizing radiation, cell death, DNA strand breaks.

Affiliation:

Institute of Automatic Control, Silesian University of Technology, Akademicka 16, 44-100, Gliwice, Stem Cell Group, Nordic EMBL Partnership, Centre for Molecular Medicine Norway (NCMM), University of Oslo, P.O. Box 1137, Blindern 0318 Oslo, Laboratory of Molecular and Cell Biology, S.P. Kapitsa Technological Research Institute, Ulyanovsk State University, Lva Tolstogo 42, 432970 Ulyanovsk, Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, Bydgoszcz 85-092, Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, Bydgoszcz 85-092, Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100, Gliwice, Department of Clinical and Experimental Medicine (IKE), Linköping University; Pathology Building, Level 9; 581 85 Linkoping

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