Connexin43 hemichannel targeting with TAT-Gap19 alleviates radiation-induced endothelial cell damage

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Connexin43 hemichannel targeting with TAT-Gap19 alleviates radiation-induced endothelial cell damage. / Ramadan, Raghda; Vromans, Els; Dornatien, Chuo Anang; Goetschalckx, Ines; Hoorelbeke, Delphine; Decrock, Elke; Baatout, Sarah; Leybaert, Luc; Aerts, An.

In: Frontiers in Pharmacology, 06.03.2020, p. 1-19.

Research output: Contribution to journalArticle

Harvard

Ramadan, R, Vromans, E, Dornatien, CA, 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, pp. 1-19. https://doi.org/10.3389/fphar.2020.00212

APA

Ramadan, R., Vromans, E., Dornatien, C. A., Goetschalckx, I., Hoorelbeke, D., Decrock, E., ... Aerts, A. (2020). Connexin43 hemichannel targeting with TAT-Gap19 alleviates radiation-induced endothelial cell damage. Frontiers in Pharmacology, 1-19. [212]. https://doi.org/10.3389/fphar.2020.00212

Vancouver

Ramadan R, Vromans E, Dornatien CA, Goetschalckx I, Hoorelbeke D, Decrock E et al. Connexin43 hemichannel targeting with TAT-Gap19 alleviates radiation-induced endothelial cell damage. Frontiers in Pharmacology. 2020 Mar 6;1-19. 212. https://doi.org/10.3389/fphar.2020.00212

Author

Ramadan, Raghda ; Vromans, Els ; Dornatien, Chuo Anang ; Goetschalckx, Ines ; Hoorelbeke, Delphine ; Decrock, Elke ; Baatout, Sarah ; Leybaert, Luc ; Aerts, An. / Connexin43 hemichannel targeting with TAT-Gap19 alleviates radiation-induced endothelial cell damage. In: Frontiers in Pharmacology. 2020 ; pp. 1-19.

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@article{9dd165696d9a46fb835c4adfb106a7b0,
title = "Connexin43 hemichannel targeting with TAT-Gap19 alleviates radiation-induced endothelial cell damage",
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.",
keywords = "Atherosclerosis, Endothelial damage, Ionizing radiation, connexin43 hemichannels, TAT-Gap19",
author = "Raghda Ramadan and Els Vromans and Dornatien, {Chuo Anang} and Ines Goetschalckx and Delphine Hoorelbeke and Elke Decrock and Sarah Baatout and Luc Leybaert and An Aerts",
note = "Score=10",
year = "2020",
month = "3",
day = "6",
doi = "10.3389/fphar.2020.00212",
language = "English",
pages = "1--19",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media",

}

RIS - Download

TY - JOUR

T1 - Connexin43 hemichannel targeting with TAT-Gap19 alleviates radiation-induced endothelial cell damage

AU - Ramadan, Raghda

AU - Vromans, Els

AU - Dornatien, Chuo Anang

AU - Goetschalckx, Ines

AU - Hoorelbeke, Delphine

AU - Decrock, Elke

AU - Baatout, Sarah

AU - Leybaert, Luc

AU - Aerts, An

N1 - Score=10

PY - 2020/3/6

Y1 - 2020/3/6

N2 - 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.

AB - 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.

KW - Atherosclerosis

KW - Endothelial damage

KW - Ionizing radiation

KW - connexin43 hemichannels

KW - TAT-Gap19

UR - https://ecm.sckcen.be/OTCS/llisapi.dll/open/38710192

U2 - 10.3389/fphar.2020.00212

DO - 10.3389/fphar.2020.00212

M3 - Article

SP - 1

EP - 19

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

M1 - 212

ER -

ID: 6807389