Gibhardt, Christine S. and Roth, Bastian and Schroeder, Indra and Fuck, Sebastian and Becker, Patrick and Jakob, Burkhard and Fournier, Claudia and Moroni, Anna and Thiel, Gerhard (2015):
X-ray irradiation activates K(+) channels via H2O2 signaling.
In: Scientific reports, p. 13861, 5, ISSN 2045-2322,
[Article]

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 Ca(2+)-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 Ca(2+) and eventually an activation of hIK channels.

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