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.

X-ray irradiation activates K+channels via H2O2 signaling / C.S. Gibhardt, B. Roth, I. Schroeder, S. Fuck, P. Becker, B. Jakob, C. Fournier, A. Moroni, G. Thiel. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 5(2015 Sep), pp. 13861.1-13861.11. [10.1038/srep13861]

X-ray irradiation activates K+channels via H2O2 signaling

I. Schroeder;A. Moroni;
2015-09

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.
Multidisciplinary
Settore BIO/04 - Fisiologia Vegetale
SCIENTIFIC REPORTS
Article (author)
File in questo prodotto:
File Dimensione Formato  
srep13861.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 1.17 MB
Formato Adobe PDF
1.17 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/346186
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 9
social impact