X-ray irradiation activates K+ channels via H2O2 signaling

Scientific Reports
Christine S GibhardtGerhard Thiel

Abstract

Ionizing radiation is a universal tool in tumor therapy but may also cause secondary cancers or cell invasiveness. These negative side effects could be causally related to the human-intermediate-conductance Ca2+-activated-K+-channel (hIK), which is activated by X-ray irradiation and affects cell proliferation and migration. To analyze the signaling cascade downstream of ionizing radiation we use genetically encoded reporters for H2O2 (HyPer) and for the dominant redox-buffer glutathione (Grx1-roGFP2) to monitor with high spatial and temporal resolution, radiation-triggered excursions of H2O2 in A549 and HEK293 cells. The data show that challenging cells with ≥1 Gy X-rays or with UV-A laser micro-irradiation causes a rapid rise of H2O2 in the nucleus and in the cytosol. This rise, which is determined by the rate of H2O2 production and glutathione-buffering, is sufficient for triggering a signaling cascade that involves an elevation of cytosolic Ca2+ and eventually an activation of hIK channels.

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Citations

May 12, 2016·European Biophysics Journal : EBJ·Benjamin StegenStephan M Huber
Sep 13, 2016·International Journal of Molecular Sciences·Lukas KlumppStephan M Huber
Jul 13, 2017·Antioxidants & Redox Signaling·Helmut Sies, Ludwig E Feinendegen
Aug 3, 2019·Micromachines·Alfonso Blázquez-Castro
May 16, 2018·Frontiers in Immunology·Patrick VoosGerhard Thiel

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Methods Mentioned

BETA
X-ray
confocal microscopy
irradiating
transfection

Software Mentioned

SypHer
LAS AF
FIJI
Andor IQ
PatchMaster
HyPer

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