Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H<sub>2</sub>S Production.

Détails

ID Serval
serval:BIB_08B1768BCDB3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H<sub>2</sub>S Production.
Périodique
Cell
Auteur(s)
Longchamp A., Mirabella T., Arduini A., MacArthur M.R., Das A., Treviño-Villarreal J.H., Hine C., Ben-Sahra I., Knudsen N.H., Brace L.E., Reynolds J., Mejia P., Tao M., Sharma G., Wang R., Corpataux J.M., Haefliger J.A., Ahn K.H., Lee C.H., Manning B.D., Sinclair D.A., Chen C.S., Ozaki C.K., Mitchell J.R.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Statut éditorial
Publié
Date de publication
22/03/2018
Peer-reviewed
Oui
Volume
173
Numéro
1
Pages
117-129.e14
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Résumé
Angiogenesis, the formation of new blood vessels by endothelial cells (ECs), is an adaptive response to oxygen/nutrient deprivation orchestrated by vascular endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best-understood trigger of VEGF expression via the transcription factor HIF1α. Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in angiogenesis is poorly characterized. Here, we identified sulfur amino acid restriction as a proangiogenic trigger, promoting increased VEGF expression, migration and sprouting in ECs in vitro, and increased capillary density in mouse skeletal muscle in vivo via the GCN2/ATF4 amino acid starvation response pathway independent of hypoxia or HIF1α. We also identified a requirement for cystathionine-γ-lyase in VEGF-dependent angiogenesis via increased hydrogen sulfide (H <sub>2</sub> S) production. H <sub>2</sub> S mediated its proangiogenic effects in part by inhibiting mitochondrial electron transport and oxidative phosphorylation, resulting in increased glucose uptake and glycolytic ATP production.
Mots-clé
Activating Transcription Factor 4/antagonists & inhibitors, Activating Transcription Factor 4/genetics, Activating Transcription Factor 4/metabolism, Amino Acids, Sulfur/deficiency, Amino Acids, Sulfur/metabolism, Animals, Cystathionine gamma-Lyase/metabolism, Disease Models, Animal, Female, Human Umbilical Vein Endothelial Cells, Humans, Hydrogen Sulfide/metabolism, Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors, Hypoxia-Inducible Factor 1, alpha Subunit/genetics, Hypoxia-Inducible Factor 1, alpha Subunit/metabolism, Ischemia/metabolism, Ischemia/pathology, Male, Mice, Mice, Inbred C57BL, Neovascularization, Physiologic, Physical Conditioning, Animal, Protein-Serine-Threonine Kinases/metabolism, RNA Interference, RNA, Small Interfering/metabolism, Vascular Endothelial Growth Factor A/genetics, Vascular Endothelial Growth Factor A/metabolism
Pubmed
Web of science
Création de la notice
29/03/2018 20:08
Dernière modification de la notice
20/08/2019 13:31
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