TY - JOUR
T1 - Calcium, oxidative stress and connexin channels, a harmonious orchestra directing the response to radiotherapy treatment?
AU - Decrock, Elke
AU - Hoorelbeke, Delphine
AU - Ramadan, Raghda
AU - Delvaeye, Tinneke
AU - De Bock, Marijke
AU - Wang, Nan
AU - Krysko, Dmitry V
AU - Baatout, Sarah
AU - Bultynck, Geert
AU - Aerts, An
AU - Vinken, Mathieu
AU - Leybaert, Luc
N1 - Score=10
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Although radiotherapy is commonly used to treat cancer, its beneficial outcome is frequently hampered by the radiation resistance of tumor cells and adverse reactions in normal tissues. Mechanisms of cell-to-cell communication and how intercellular signals are translated into cellular responses, have become topics of intense investigation, particularly within the field of radiobiology. A substantial amount of evidence is available demonstrating that both gap junctional and paracrine communication pathways can propagate radiation-induced biological effects at the intercellular level, commonly referred to as radiation-induced bystander effects (RIBE). Multiple molecular signaling mechanisms involving oxidative stress, kinases, inflammatory molecules, and Ca2+ are postulated to contribute to RIBE. Ca2+ is a highly versatile and ubiquitous second messenger that regulates diverse cellular processes via the interaction with various signaling cascades. It furthermore provides a fast system for the dissemination of information at the intercellular level. Channels formed by transmembrane connexin (Cx) proteins, i.e. hemichannels and gap junction channels, can mediate the cell-to-cell propagation of increases in intracellular Ca2+ by ministering paracrine and direct cell-cell communication, respectively. We here review current knowledge on radiation-induced signaling mechanisms in irradiated and bystander cells, particularly focusing on the contribution of oxidative stress, Ca2+ and Cx channels. By illustrating the tight interplay between these different partners, we provide a conceptual framework for intercellular Ca2+ signaling as a key player in modulating the RIBE and the overall response to radiation.
Copyright � 2017 Elsevier B.V. All rights reserved.
AB - Although radiotherapy is commonly used to treat cancer, its beneficial outcome is frequently hampered by the radiation resistance of tumor cells and adverse reactions in normal tissues. Mechanisms of cell-to-cell communication and how intercellular signals are translated into cellular responses, have become topics of intense investigation, particularly within the field of radiobiology. A substantial amount of evidence is available demonstrating that both gap junctional and paracrine communication pathways can propagate radiation-induced biological effects at the intercellular level, commonly referred to as radiation-induced bystander effects (RIBE). Multiple molecular signaling mechanisms involving oxidative stress, kinases, inflammatory molecules, and Ca2+ are postulated to contribute to RIBE. Ca2+ is a highly versatile and ubiquitous second messenger that regulates diverse cellular processes via the interaction with various signaling cascades. It furthermore provides a fast system for the dissemination of information at the intercellular level. Channels formed by transmembrane connexin (Cx) proteins, i.e. hemichannels and gap junction channels, can mediate the cell-to-cell propagation of increases in intracellular Ca2+ by ministering paracrine and direct cell-cell communication, respectively. We here review current knowledge on radiation-induced signaling mechanisms in irradiated and bystander cells, particularly focusing on the contribution of oxidative stress, Ca2+ and Cx channels. By illustrating the tight interplay between these different partners, we provide a conceptual framework for intercellular Ca2+ signaling as a key player in modulating the RIBE and the overall response to radiation.
Copyright � 2017 Elsevier B.V. All rights reserved.
KW - Ionizing radioation
KW - Calcium
KW - Oxidative stress
KW - Connexin hemichannel
KW - gap junction
KW - Bystander effect
UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/26103753
UR - https://www.ncbi.nlm.nih.gov/pubmed/?term=decrock+baatout
U2 - 10.1016/j.bbamcr.2017.02.007
DO - 10.1016/j.bbamcr.2017.02.007
M3 - Literature review
VL - 1864
SP - 1099
EP - 1120
JO - Biochimica et Biophysica Acta
JF - Biochimica et Biophysica Acta
IS - 6
ER -