Key result
X-ray irradiation of ≥1 Gy causes a rapid rise of H2O2 in the nucleus and cytosol, which triggers an elevation of cytosolic Ca2+ and activates hIK channels.
Why the study?
Does X-ray irradiation activate hIK channels via H2O2 signaling in A549 and HEK293 cells?
Does X-ray irradiation activate hIK channels via H2O2 signaling in A549 and HEK293 cells?
X-ray irradiation triggers a rapid rise in intracellular H2O2, leading to elevated cytosolic Ca2+ and activation of hIK channels, which may contribute to radiation-induced secondary cancers or cell invasiveness.
May promote radiation-induced cancer cell invasiveness via hIK; hypothesis-generating, requires in vivo validation before any clinical consideration.
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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Gibhardt et al. (2015) studied Radiation-induced cellular signaling. X-ray irradiation vs. Unirradiated cells was evaluated on Intracellular H2O2 concentration (HyPer ratio F488/405). X-ray irradiation of ≥1 Gy causes a rapid rise of H2O2 in the nucleus and cytosol, which triggers an elevation of cytosolic Ca2+ and activates hIK channels.
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