Mutation of Arginine 264 on ERα (Estrogen Receptor Alpha) Selectively Abrogates the Rapid Signaling of Estradiol in the Endothelium Without Altering Fertility.
Animals
Atherosclerosis
/ metabolism
Carotid Artery Injuries
/ drug therapy
Cell Proliferation
/ drug effects
Endothelium, Vascular
/ drug effects
Enzyme Activation
Estradiol
/ pharmacology
Estrogen Receptor alpha
/ agonists
Estrogen Replacement Therapy
Estrogens
/ pharmacology
Estrous Cycle
/ drug effects
Female
Fertility
/ drug effects
Male
Mesenteric Arteries
/ drug effects
Mice, Inbred C57BL
Nitric Oxide Synthase Type III
/ metabolism
Ovariectomy
Point Mutation
Re-Epithelialization
/ drug effects
Signal Transduction
Time Factors
Uterus
/ drug effects
Vascular Remodeling
/ drug effects
Vasodilation
/ drug effects
arginine
endothelium
estradiol
estrogen receptor alpha
fertility
mice
vascular diseases
Journal
Arteriosclerosis, thrombosis, and vascular biology
ISSN: 1524-4636
Titre abrégé: Arterioscler Thromb Vasc Biol
Pays: United States
ID NLM: 9505803
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
pubmed:
10
7
2020
medline:
8
10
2020
entrez:
10
7
2020
Statut:
ppublish
Résumé
ERα (estrogen receptor alpha) exerts nuclear genomic actions and also rapid membrane-initiated steroid signaling. The mutation of the cysteine 451 into alanine in vivo has recently revealed the key role of this ERα palmitoylation site on some vasculoprotective actions of 17β-estradiol (E2) and fertility. Here, we studied the in vivo role of the arginine 260 of ERα which has also been described to be involved in its E2-induced rapid signaling with PI-3K (phosphoinositide 3-kinase) as well as G protein in cultured cell lines. Approach and Results: We generated a mouse model harboring a point mutation of the murine counterpart of this arginine into alanine (R264A-ERα). In contrast to the These data underline the exquisite role of arginine 264 of ERα for endothelial membrane-initiated steroid signaling effects of E2 but not for nuclear/genomic actions. This provides the first model of fertile mouse with no overt endocrine abnormalities with specific loss-of-function of rapid ERα signaling in vascular functions.
Identifiants
pubmed: 32640903
doi: 10.1161/ATVBAHA.120.314159
doi:
Substances chimiques
Esr1 protein, mouse
0
Estrogen Receptor alpha
0
Estrogens
0
Estradiol
4TI98Z838E
Nitric Oxide Synthase Type III
EC 1.14.13.39
Nos3 protein, mouse
EC 1.14.13.39
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM