Inhibiting astrocyte connexin-43 hemichannels blocks radiation-induced vesicular VEGF-A release and blood-brain barrier dysfunction
- Author
- Steffi Schumacher (UGent) , Hanane Tahiri (UGent) , Pascal Ezan, Nathalie Rouach, Katja Witschas (UGent) and Luc Leybaert (UGent)
- Organization
- Project
- Abstract
- Therapeutic brain irradiation with ionizing radiation exerts multiple side effects including barrier leakage that disturbs glial-neuronal functioning and may affect cognition. Astrocytes contribute to barrier leakage by endfeet release of various vasoactive substances acting on capillary endothelial cells forming the barrier. Here, we investigated X-ray effects on astrocytic vesicular transport in mice and determined whether interfering with astrocyte connexins affects radiation-induced barrier leakage. We found that astrocytic VEGF-A-loaded VAMP3 vesicles drastically reorganize starting from 6 h post-irradiation and move in a calcium- and Cx43-dependent manner towards endfeet where VEGF-A is released, provoking barrier leakage. Vesicular transport activation, VEGF-A release and leakage 24 h post-irradiation were all potently inhibited by astrocytic Cx43 KO, Cx43S255/262/279/282A (MK4) mutant mice and TATGap19 inhibition of Cx43 hemichannel opening. Astrocyte VEGF release is a major player in complications of brain irradiation, which can be mitigated by anti-VEGF treatments. Targeting Cx43 hemichannels allows to prevent astrocyte VEGF release at an early stage after brain irradiation.
- Keywords
- ionizing radiation, connexin, calcium, brain, blood-barrier, astrocyte
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HCHVEX5QNJAYX9G0WSR4S576
- MLA
- Schumacher, Steffi, et al. “Inhibiting Astrocyte Connexin-43 Hemichannels Blocks Radiation-Induced Vesicular VEGF-A Release and Blood-Brain Barrier Dysfunction.” GLIA, vol. 72, no. 1, 2024, pp. 34–50, doi:10.1002/glia.24460.
- APA
- Schumacher, S., Tahiri, H., Ezan, P., Rouach, N., Witschas, K., & Leybaert, L. (2024). Inhibiting astrocyte connexin-43 hemichannels blocks radiation-induced vesicular VEGF-A release and blood-brain barrier dysfunction. GLIA, 72(1), 34–50. https://doi.org/10.1002/glia.24460
- Chicago author-date
- Schumacher, Steffi, Hanane Tahiri, Pascal Ezan, Nathalie Rouach, Katja Witschas, and Luc Leybaert. 2024. “Inhibiting Astrocyte Connexin-43 Hemichannels Blocks Radiation-Induced Vesicular VEGF-A Release and Blood-Brain Barrier Dysfunction.” GLIA 72 (1): 34–50. https://doi.org/10.1002/glia.24460.
- Chicago author-date (all authors)
- Schumacher, Steffi, Hanane Tahiri, Pascal Ezan, Nathalie Rouach, Katja Witschas, and Luc Leybaert. 2024. “Inhibiting Astrocyte Connexin-43 Hemichannels Blocks Radiation-Induced Vesicular VEGF-A Release and Blood-Brain Barrier Dysfunction.” GLIA 72 (1): 34–50. doi:10.1002/glia.24460.
- Vancouver
- 1.Schumacher S, Tahiri H, Ezan P, Rouach N, Witschas K, Leybaert L. Inhibiting astrocyte connexin-43 hemichannels blocks radiation-induced vesicular VEGF-A release and blood-brain barrier dysfunction. GLIA. 2024;72(1):34–50.
- IEEE
- [1]S. Schumacher, H. Tahiri, P. Ezan, N. Rouach, K. Witschas, and L. Leybaert, “Inhibiting astrocyte connexin-43 hemichannels blocks radiation-induced vesicular VEGF-A release and blood-brain barrier dysfunction,” GLIA, vol. 72, no. 1, pp. 34–50, 2024.
@article{01HCHVEX5QNJAYX9G0WSR4S576,
abstract = {{Therapeutic brain irradiation with ionizing radiation exerts multiple side effects including barrier leakage that disturbs glial-neuronal functioning and may affect cognition. Astrocytes contribute to barrier leakage by endfeet release of various vasoactive substances acting on capillary endothelial cells forming the barrier. Here, we investigated X-ray effects on astrocytic vesicular transport in mice and determined whether interfering with astrocyte connexins affects radiation-induced barrier leakage. We found that astrocytic VEGF-A-loaded VAMP3 vesicles drastically reorganize starting from 6 h post-irradiation and move in a calcium- and Cx43-dependent manner towards endfeet where VEGF-A is released, provoking barrier leakage. Vesicular transport activation, VEGF-A release and leakage 24 h post-irradiation were all potently inhibited by astrocytic Cx43 KO, Cx43S255/262/279/282A (MK4) mutant mice and TATGap19 inhibition of Cx43 hemichannel opening. Astrocyte VEGF release is a major player in complications of brain irradiation, which can be mitigated by anti-VEGF treatments. Targeting Cx43 hemichannels allows to prevent astrocyte VEGF release at an early stage after brain irradiation.}},
author = {{Schumacher, Steffi and Tahiri, Hanane and Ezan, Pascal and Rouach, Nathalie and Witschas, Katja and Leybaert, Luc}},
issn = {{0894-1491}},
journal = {{GLIA}},
keywords = {{ionizing radiation,connexin,calcium,brain,blood-barrier,astrocyte}},
language = {{eng}},
number = {{1}},
pages = {{34--50}},
title = {{Inhibiting astrocyte connexin-43 hemichannels blocks radiation-induced vesicular VEGF-A release and blood-brain barrier dysfunction}},
url = {{http://doi.org/10.1002/glia.24460}},
volume = {{72}},
year = {{2024}},
}
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