Inhibition of decidual IGF-1 signaling in response to hypoxia and leucine deprivation is mediated by mTOR and AAR pathways and increased IGFBP-1 phosphorylation.
Amino Acid Transport Systems
/ metabolism
Casein Kinase II
/ metabolism
Cell Hypoxia
/ physiology
Cells, Cultured
Decidua
/ drug effects
Down-Regulation
/ drug effects
Female
Humans
Insulin-Like Growth Factor Binding Protein 1
/ metabolism
Leucine
/ deficiency
Phosphorylation
Receptors, Amino Acid
/ metabolism
Signal Transduction
/ drug effects
Sirolimus
/ pharmacology
TOR Serine-Threonine Kinases
/ metabolism
Biological availability
Humans
Intrauterine growth restriction
Maternal-fetal exchange
Pregnancy
Journal
Molecular and cellular endocrinology
ISSN: 1872-8057
Titre abrégé: Mol Cell Endocrinol
Pays: Ireland
ID NLM: 7500844
Informations de publication
Date de publication:
15 07 2020
15 07 2020
Historique:
received:
15
01
2020
revised:
10
05
2020
accepted:
10
05
2020
pubmed:
6
6
2020
medline:
28
5
2021
entrez:
6
6
2020
Statut:
ppublish
Résumé
Decidual mechanistic target of rapamycin (mTOR) is inhibited, amino acid response (AAR) and protein kinase CK2 are activated, and IGF (insulin-like growth factor) binding protein (IGFBP)-1 is hyperphosphorylated in human intrauterine growth restriction (IUGR). Using decidualized human immortalized endometrial stromal cells (HIESC), we hypothesized that hypoxia and leucine deprivation causing inhibition of decidual IGF-1 signaling is mediated by mTOR, AAR, CK2 and IGFBP-1 phosphorylation. Mass spectrometry demonstrated that hypoxia (1% O
Identifiants
pubmed: 32502935
pii: S0303-7207(20)30165-9
doi: 10.1016/j.mce.2020.110865
pii:
doi:
Substances chimiques
Amino Acid Transport Systems
0
IGFBP1 protein, human
0
Insulin-Like Growth Factor Binding Protein 1
0
Receptors, Amino Acid
0
MTOR protein, human
EC 2.7.1.1
Casein Kinase II
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Leucine
GMW67QNF9C
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110865Subventions
Organisme : NICHD NIH HHS
ID : R01 HD089980
Pays : United States
Informations de copyright
Copyright © 2020. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors report no conflicts of interest related to this work.