Non-genomic mechanisms in the estrogen regulation of glycolytic protein levels in endothelial cells.
GPER
PFKFB3
USP19
endothelium
estrogen
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
06
05
2020
revised:
07
07
2020
accepted:
15
07
2020
pubmed:
7
8
2020
medline:
12
3
2021
entrez:
7
8
2020
Statut:
ppublish
Résumé
Few studies have explored the mechanisms coupling estrogen signals to metabolic demand in endothelial cells. We recently showed that 17β-estradiol (E2) triggers angiogenesis via the membrane G-protein coupled estrogen receptor (GPER) and the key glycolytic protein PFKFB3 as a downstream effector. We herein investigated whether estrogenic agents regulate the stability and/or degradation of glycolytic proteins in human umbilical vein endothelial cells (HUVECs). Similarly to E2, the GPER selective agonist G1 rapidly increased PFKFB3 protein amounts, without affecting mRNA levels. In the presence of cycloheximide, E2 and G1 treatment counteracted PFKFB3 degradation over time, whereas E2-induced PFKFB3 stabilization was abolished by the GPER antagonist G15. Inhibitors of selective SCF E3 ubiquitin ligase (SMER-3) and proteasome (MG132) rapidly increased PFKFB3 protein levels. Accordingly, ubiquitin-bound PFKFB3 was lower in E2- or G1-treated HUVECs. Both agents increased deubiquitinase USP19 levels through GPER signaling. Notably, USP 19 siRNA decreased PFKFB3 levels and abolished E2- and G1-mediated HUVEC tubularization. Finally, E2 and G1 treatments rapidly enhanced glucose transporter GLUT1 levels via GPER independent of transcriptional activation. These findings provide new evidence on mechanisms coupling estrogen signals with the glycolytic program in endothelium and unravel the role of USP19 as a target of the pro-angiogenic effect of estrogenic agents.
Identifiants
pubmed: 32757462
doi: 10.1096/fj.202001130R
doi:
Substances chimiques
GPER1 protein, human
0
Glucose Transporter Type 1
0
Receptors, Estrogen
0
Receptors, G-Protein-Coupled
0
SLC2A1 protein, human
0
Estradiol
4TI98Z838E
PFKFB3 protein, human
EC 2.7.1.105
Phosphofructokinase-2
EC 2.7.1.105
Endopeptidases
EC 3.4.-
USP19 protein, human
EC 3.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12768-12784Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
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