Bystander signaling via oxidative metabolism

Abstract

The radiation-induced bystander effect (RIBE) is the initiation of biological end points in cells (bystander cells) that are not directly traversed by an incident-radiation track, but are in close proximity to cells that are receiving the radiation. RIBE has been indicted of causing DNA damage via oxidative stress, besides causing direct damage, inducing tumorigenesis, producing micronuclei, and causing apoptosis. RIBE is regulated by signaling proteins that are either endogenous or secreted by cells as a means of communication between cells, and can activate intracellular or intercellular oxidative metabolism that can further trigger signaling pathways of inflammation. Bystander signals can pass through gap junctions in attached cell lines, while the suspended cell lines transmit these signals via hormones and soluble proteins. This review provides the background information on how reactive oxygen species (ROS) act as bystander signals. Although ROS have a very short half-life and have a nanometer-scale sphere of influence, the wide variety of ROS produced via various sources can exert a cumulative effect, not only in forming DNA adducts but also setting up signaling pathways of inflammation, apoptosis, cell-cycle arrest, aging, and even tumorigenesis. This review outlines the sources of the bystander effect linked to ROS in a cell, and provides methods of investigation for researchers who would like to pursue this field of science.

Hydroxyurea‐induced senescent peripheral blood mesenchymal stromal cells inhibit bystander cell proliferation of JAK2V617F‐positive human erythroleukemia cells

“…SASPs comprise an array of soluble factors with diverse biological activities, which may influence the fate of neighboring cells via bystander effects . These paracrine effects include growth inhibition and DNA damage induction, which can be a result of SASPs expression of such as TNF‐α, nitric oxide, ROS, and TGF‐β1, among others .…”

“…Although, in some specific situations, ROS may promote cell proliferation, they can act as cytostatic/cytotoxic agents. In fact, most of the anticancer drugs affect cancer cell proliferation and survival by inducing the generation of elevated ROS levels . Both H 2 O 2 and its dismutation products reduce cancer cell proliferation, which can be avoided by the addition of catalase to cell cultures.…”

Suppression of SESN1 reduces cisplatin and hyperthermia resistance through increasing reactive oxygen species (ROS) in human maxillary cancer cells

“…ROS activate the mitochondrial pathway by inducing the release of cytochrome c from the mitochondria and the formation of the apoptosome complex with Apaf-1 and pro-caspase-9 in the cytoplasm. Caspase-9 is activated at the apoptosome, activates caspase-3 and cleaves PARP, resulting in apoptosis ( Figure 5) [26,27]. Various cancer cells have strong antioxidant defences to endure elevated ROS and to avoid apoptosis [28].…”

Cx43 channels and signaling via IP3/Ca2+, ATP, and ROS/NO propagate radiation-induced DNA damage to non-irradiated brain microvascular endothelial cells

“…All things considered, we propose that irradiation activates ATP-ROS-Ca 2+ -signal signaling with ROS as the primary generated signal, which, given its very short lifetime (10 −9 s for the hydroxyl radical 23 ) and diffusion distance (4 nm for the hydroxyl radical 24 ) 72 , has a limited role in long-range bystander consequences. Ca 2+ hereby acts as an intracellular and ATP as an extracellular propagator of bystander effects.…”