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

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

Volume: 13 Issue: 5

Author(s): Magdalena Skonieczna, Artur Cieslar-Pobuda, Yuriy Saenko, Marek Foksinski, Ryszard Olinski, Joanna Rzeszowska-Wolny and Emilia Wiechec*

Affiliation:

• Department of Clinical and Experimental Medicine (IKE), Linköping University; Pathology Building, Level 9; 581 85 Linkoping,Sweden

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.

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.

Cite this article as:

Skonieczna Magdalena, Cieslar-Pobuda Artur, Saenko Yuriy, Foksinski Marek, Olinski Ryszard, Rzeszowska-Wolny Joanna and Wiechec Emilia*, The Impact of DIDS-Induced Inhibition of Voltage-Dependent Anion Channels (VDAC) on Cellular Response of Lymphoblastoid Cells to Ionizing Radiation, Medicinal Chemistry 2017; 13 (5) . https://dx.doi.org/10.2174/1573406413666170421102353

DOI https://dx.doi.org/10.2174/1573406413666170421102353	Print ISSN 1573-4064
Publisher Name Bentham Science Publisher	Online ISSN 1875-6638