Related Experiment Video

Updated: Apr 4, 2026

A Co-culture Method to Investigate the Crosstalk Between X-ray Irradiated Caco-2 Cells and PBMC
11:40

A Co-culture Method to Investigate the Crosstalk Between X-ray Irradiated Caco-2 Cells and PBMC

Published on: January 30, 2018

13.8K

X-ray irradiation activates K+ channels via H2O2 signaling

Christine S Gibhardt1, Bastian Roth1, Indra Schroeder1

  • 1Department of Biology, Membrane Biophysics, Technische Universität Darmstadt, Schnittspahnstrasse 3, 64287 Darmstadt, Germany.

Scientific Reports
|September 10, 2015
PubMed

Insights

Ionizing radiation increases hydrogen peroxide (H2O2) levels, activating signaling pathways that lead to the human-intermediate-conductance Ca2+-activated-K+ channel (hIK) activation, potentially causing negative side effects in tumor therapy.

Area of Science:

  • Cellular Biology
  • Radiation Oncology
  • Biophysics

Background:

  • Ionizing radiation is a cornerstone of cancer treatment but can induce detrimental effects like secondary cancers and increased cell invasiveness.
  • The human-intermediate-conductance Ca2+-activated-K+ channel (hIK) is implicated in radiation-induced side effects, as it is activated by X-ray irradiation and influences cell proliferation and migration.

Purpose of the Study:

  • To elucidate the signaling cascade initiated by ionizing radiation.
  • To investigate the role of hydrogen peroxide (H2O2) and glutathione in radiation-induced cellular responses.
  • To understand the activation mechanism of the hIK channel following irradiation.

Main Methods:

  • Utilized genetically encoded reporters, HyPer for H2O2 and Grx1-roGFP2 for glutathione, to monitor redox changes with high spatial and temporal resolution.
  • Applied X-ray irradiation (≥1 Gy) and UV-A laser micro-irradiation to A549 and HEK293 cells.
  • Measured intracellular H2O2 levels in the nucleus and cytosol, alongside cytosolic Ca2+ concentrations and hIK channel activity.

Main Results:

  • X-ray and UV-A laser irradiation triggered a rapid increase in H2O2 levels within both the nucleus and cytosol of treated cells.
  • The observed H2O2 surge was dependent on the production rate and the buffering capacity of glutathione.
  • This radiation-induced H2O2 elevation was sufficient to initiate a signaling cascade, leading to increased cytosolic Ca2+ and subsequent activation of hIK channels.

Conclusions:

  • Ionizing radiation provokes a rapid oxidative stress response characterized by increased H2O2 production.
  • The glutathione redox buffer system plays a critical role in modulating radiation-induced H2O2 levels.
  • The H2O2-mediated signaling cascade culminates in the activation of hIK channels, offering a potential target for mitigating radiation therapy side effects.

More Related Videos

Quantification of γH2AX Foci in Response to Ionising Radiation06:53

Quantification of γH2AX Foci in Response to Ionising Radiation

Published on: April 6, 2010

21.2K
Evaluation of the Spatial Distribution of γH2AX following Ionizing Radiation09:28

Evaluation of the Spatial Distribution of γH2AX following Ionizing Radiation

Published on: August 7, 2010

13.2K

Related Concept Videos

X-ray Imaging01:24

X-ray Imaging

German physicist Wilhelm Röntgen (1845–1923) was experimenting with electrical current when he discovered that a mysterious and invisible "ray" would pass through his flesh but leave an outline of his bones on a screen coated with a metal compound. In 1895, Röntgen made the first durable record of the internal parts of a living human: an "X-ray" image (as it came to be called) of his wife’s hand. Scientists worldwide quickly began their own experiments with...
11.1K
Endocrine Signaling01:45

Endocrine Signaling

Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
69.4K
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
7.0K
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
45.6K
Secondary Messengers in Hormone Action01:26

Secondary Messengers in Hormone Action

Water-soluble hormones cannot cross the plasma membrane, so they rely on protein receptors that span the membrane to trigger intracellular signaling pathways. These pathways then activate second messengers inside the cell, including cAMP or calcium ions.
Many hormones bind to transmembrane G protein-coupled receptors that connect to regulatory G proteins. These G proteins can then activate enzymes such as adenylyl cyclase or phospholipase C. Adenylyl cyclase converts ATP to cAMP, activating...
6.2K
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
113