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Ramadan R, Vromans E, Anang DC, et al. Connexin43 Hemichannel Targeting With TAT-Gap19 Alleviates Radiation-Induced Endothelial Cell Damage. Front Pharmacol. 2020;11:212doi: 10.3389/fphar.2020.00212.
Ramadan, R., Vromans, E., Anang, D. C., Goetschalckx, I., Hoorelbeke, D., Decrock, E., Baatout, S., Leybaert, L., & Aerts, A. (2020). Connexin43 Hemichannel Targeting With TAT-Gap19 Alleviates Radiation-Induced Endothelial Cell Damage. Frontiers in pharmacology, 11212. https://doi.org/10.3389/fphar.2020.00212
Ramadan, Raghda, et al. "Connexin43 Hemichannel Targeting With TAT-Gap19 Alleviates Radiation-Induced Endothelial Cell Damage." Frontiers in pharmacology vol. 11 (2020): 212. doi: https://doi.org/10.3389/fphar.2020.00212
Ramadan R, Vromans E, Anang DC, Goetschalckx I, Hoorelbeke D, Decrock E, Baatout S, Leybaert L, Aerts A. Connexin43 Hemichannel Targeting With TAT-Gap19 Alleviates Radiation-Induced Endothelial Cell Damage. Front Pharmacol. 2020 Mar 05;11:212. doi: 10.3389/fphar.2020.00212. eCollection 2020. PMID: 32210810; PMCID: PMC7066501.
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Front Pharmacol. 2020 Mar 05;11:212. doi: 10.3389/fphar.2020.00212. eCollection 2020.

Connexin43 Hemichannel Targeting With TAT-Gap19 Alleviates Radiation-Induced Endothelial Cell Damage.

Frontiers in pharmacology

Raghda Ramadan, Els Vromans, Dornatien Chuo Anang, Ines Goetschalckx, Delphine Hoorelbeke, Elke Decrock, Sarah Baatout, Luc Leybaert, An Aerts

Affiliations

  1. Radiobiology Unit, Belgian Nuclear Research Centre (SCK•CEN), Mol, Belgium.
  2. Department of Fundamental and Basic Medical Sciences, Physiology Group, Ghent University, Ghent, Belgium.
  3. Centre for Environmental Health Sciences, Hasselt University, Hasselt, Belgium.
  4. Biomedical Research Institute and Transnational University of Limburg, Hasselt University, Hasselt, Belgium.
  5. Protein Chemistry, Proteomics and Epigenetic Signaling Group, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
  6. Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.

PMID: 32210810 PMCID: PMC7066501 DOI: 10.3389/fphar.2020.00212

Abstract

BACKGROUND: Emerging evidence indicates an excess risk of late occurring cardiovascular diseases, especially atherosclerosis, after thoracic cancer radiotherapy. Ionizing radiation (IR) induces cellular effects which may induce endothelial cell dysfunction, an early marker for atherosclerosis. In addition, intercellular communication through channels composed of transmembrane connexin proteins (Cxs), i.e. Gap junctions (direct cell-cell coupling) and hemichannels (paracrine release/uptake pathway) can modulate radiation-induced responses and therefore the atherosclerotic process. However, the role of endothelial hemichannel in IR-induced atherosclerosis has never been described before.

MATERIALS AND METHODS: Telomerase-immortalized human Coronary Artery/Microvascular Endothelial cells (TICAE/TIME) were exposed to X-rays (0.1 and 5 Gy). Production of reactive oxygen species (ROS), DNA damage, cell death, inflammatory responses, and senescence were assessed with or without applying a Cx43 hemichannel blocker (TAT-Gap19).

RESULTS: We report here that IR induces an increase in oxidative stress, cell death, inflammatory responses (IL-8, IL-1β, VCAM-1, MCP-1, and Endothelin-1) and premature cellular senescence in TICAE and TIME cells. These effects are significantly reduced in the presence of the Cx43 hemichannel-targeting peptide TAT-Gap19.

CONCLUSION: Our findings suggest that endothelial Cx43 hemichannels contribute to various IR-induced processes, such as ROS, cell death, inflammation, and senescence, resulting in an increase in endothelial cell damage, which could be protected by blocking these hemichannels. Thus, targeting Cx43 hemichannels may potentially exert radioprotective effects.

Copyright © 2020 Ramadan, Vromans, Anang, Goetschalckx, Hoorelbeke, Decrock, Baatout, Leybaert and Aerts.

Keywords: TAT-Gap19; atherosclerosis; connexin43 hemichannels; endothelial damage; ionizing radiation

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