Tyramine mediates radiation-induced bystander effects
Abstract
Radiation-induced bystander effects (RIBEs) compromise radioprotection and radiotherapy by propagating damage to non-irradiated cells; however, the mediators and underlying circuitry remain incompletely defined. Using localised UV irradiation as the primary experimental system and localised X-ray irradiation as a supportive test in an in vivo Caenorhabditis elegans model, we identify tyramine, a trace amine structurally and functionally related to adrenaline/noradrenaline, as a neuron-derived mediator of RIBEs. Tyramine released from tyraminergic RIM neurons activates TYRA-3, a tyramine-responsive adrenergic-like GPCR related to vertebrate adrenergic receptors. This neuron-to-intestine signal promotes secretion of the insulin-like peptide INS-5, aberrantly engages the DAF-2/insulin signalling pathway (IIS), and triggers endoplasmic reticulum stress, DNA damage responses, and embryonic lethality in non-irradiated tissues. These findings reveal a neuro–intestinal–germline axis that orchestrates RIBEs and uncover an unanticipated role for adrenaline-like signalling. Our work provides a conceptual framework for systematically discovering additional RIBE mediators and identifies pathway components for future evaluation as radioprotective or radiotherapy-modifying targets.
Related
- Proton-Induced Bystander Signaling Drives Cell-Type-Specific Proteomic Remodeling in Chondrocytes and Endothelial Cells
- Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression
- Notch signaling pathway mediates anti-inflammatory effects of vagus nerve stimulation during lipopolysaccharide-induced acute kidney injury
- TGF-alpha/EGFR signalling mediates retinoic acid-induced lung repair
- p66Shc mediates SUMO2-induced endothelial dysfunction.
BibTeX
@article{huang2026tyramine,
title = {{Tyramine mediates radiation-induced bystander effects}},
author = {Zirui Huang and Jiane-Kang Liu and Wenyuan He and Longnong You and Lizhu Zhang and Yongsheng Chen and Yaoyong Zeng and Yuxin Guo and Haiyang Yu and Junbu Li and Shiming Li and Xinyu Tao and Peng Falcon Liu and Bin Liu and Chao Zhao and Lingjun Zheng},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78815-z},
url = {https://www.nature.com/articles/s41467-026-78815-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tyramine mediates radiation-induced bystander effects
AU - Zirui Huang
AU - Jiane-Kang Liu
AU - Wenyuan He
AU - Longnong You
AU - Lizhu Zhang
AU - Yongsheng Chen
AU - Yaoyong Zeng
AU - Yuxin Guo
AU - Haiyang Yu
AU - Junbu Li
AU - Shiming Li
AU - Xinyu Tao
AU - Peng Falcon Liu
AU - Bin Liu
AU - Chao Zhao
AU - Lingjun Zheng
PY - 2026
DA - 2026/10/23
JO - Nature Communications
DO - 10.1038/s41467-026-78815-z
UR - https://www.nature.com/articles/s41467-026-78815-z
AB - Radiation-induced bystander effects (RIBEs) compromise radioprotection and radiotherapy by propagating damage to non-irradiated cells; however, the mediators and underlying circuitry remain incompletely defined. Using localised UV irradiation as the primary experimental system and localised X-ray irradiation as a supportive test in an in vivo Caenorhabditis elegans model, we identify tyramine, a trace amine structurally and functionally related to adrenaline/noradrenaline, as a neuron-derived mediator of RIBEs. Tyramine released from tyraminergic RIM neurons activates TYRA-3, a tyramine-responsive adrenergic-like GPCR related to vertebrate adrenergic receptors. This neuron-to-intestine signal promotes secretion of the insulin-like peptide INS-5, aberrantly engages the DAF-2/insulin signalling pathway (IIS), and triggers endoplasmic reticulum stress, DNA damage responses, and embryonic lethality in non-irradiated tissues. These findings reveal a neuro–intestinal–germline axis that orchestrates RIBEs and uncover an unanticipated role for adrenaline-like signalling. Our work provides a conceptual framework for systematically discovering additional RIBE mediators and identifies pathway components for future evaluation as radioprotective or radiotherapy-modifying targets.
SN - 2041-1723
ER -