Academic Journal
Sphingosine-1-phosphate activates the AKT pathway to protect small intestines from radiation-induced endothelial apoptosis
| العنوان: | Sphingosine-1-phosphate activates the AKT pathway to protect small intestines from radiation-induced endothelial apoptosis |
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| المؤلفون: | Bonnaud, S., Niaudet, C., Legoux, F., Corre, I., Delpon, G., Saulquin, X., Fuks, Z., Gaugler, M.-H., Kolesnick, R., Paris, F. |
| المساهمون: | Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre Régional de Lutte Contre le Cancer Nantes-Atlantique, Memorial Sloan-Kettering Cancer Center New York, NY, États-Unis (MSKCC), Institut de Radioprotection et de Sûreté Nucléaire (IRSN) |
| المصدر: | ISSN: 0008-5472. |
| بيانات النشر: | HAL CCSD American Association for Cancer Research |
| سنة النشر: | 2010 |
| المجموعة: | Université de Nantes: HAL-UNIV-NANTES |
| مصطلحات موضوعية: | inhibitory guanine nucleotide binding protein, pertussis toxin, protein kinase B, sphingosine 1 phosphate, animal cell, animal experiment, animal model, apoptosis, article, B lymphocyte, cell protection, cell type, controlled study, endothelium cell, endothelium injury, gastrointestinal disease, in vitro study, in vivo study, intestine cell, intestine epithelium cell, irradiation, male, mouse, nonhuman, overall survival, priority journal, radiation dose, radiation enteropathy, radiation protection, signal transduction |
| الوصف: | cited By 56 ; International audience ; A previous in vitro study showed that sphingosine-1-phosphate (S1P), a ceramide antagonist, preserved endothelial cells in culture from radiation-induced apoptosis. We proposed to validate the role of S1P in tissue radioprotection by inhibiting acute gastrointestinal (GI) syndrome induced by endothelial cell apoptosis after high dose of radiation. Retro-orbital S1P was injected in mice exposed to 15 Gy, a dose-inducing GI syndrome within 10 days. Overall survival and apoptosis on intestines sections were studied. Intestinal cell type targeted by S1P and early molecular survival pathways were researched using irradiated in vitro cell models and in vivo mouse models. We showed that retro-orbital S1P injection before irradiation prevented GI syndrome by inhibiting endothelium collapse. We defined endothelium as a specific therapeutic target because only these cells and not intestinal epithelial cells, or B and T lymphocytes, were protected. Pharmacologic approaches using AKT inhibitor and pertussis toxin established that S1P affords endothelial cell protection in vitro and in vivo through a mechanism involving AKT and 7-pass transmembrane receptors coupled to Gi proteins. Our results provide strong pharmacologic and mechanistic proofs that S1P protects endothelial cells against acute radiation enteropathy. ©2010 AACR. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1158/0008-5472.CAN-10-2043 |
| الاتاحة: | https://hal.science/hal-02975630 https://doi.org/10.1158/0008-5472.CAN-10-2043 |
| رقم الانضمام: | edsbas.48962471 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1158/0008-5472.CAN-10-2043 |
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