AMP-Kinase Dysfunction Alters Notch Ligands to Impair Angiogenesis in Neonatal Pulmonary Hypertension.
AMP-Activated Protein Kinase Kinases
Animals
Animals, Newborn
Biphenyl Compounds
Ductus Arteriosus
/ embryology
Electron Transport
Endothelial Cells
/ enzymology
Enzyme Activation
Female
Hypertension, Pulmonary
/ enzymology
Intracellular Signaling Peptides and Proteins
/ metabolism
Jagged-1 Protein
/ metabolism
Ligands
Lung
/ pathology
Membrane Proteins
/ metabolism
Metformin
/ pharmacology
Mitochondria
/ metabolism
Neovascularization, Pathologic
/ drug therapy
Persistent Fetal Circulation Syndrome
/ drug therapy
Phosphorylation
Pregnancy
Protein Kinases
/ metabolism
Pyrones
/ pharmacology
Receptors, Notch
/ metabolism
Sheep
Thiophenes
/ pharmacology
Threonine
/ metabolism
Transfection
endothelial cells
liver kinase B1
mitochondrial function
notch signaling
Journal
American journal of respiratory cell and molecular biology
ISSN: 1535-4989
Titre abrégé: Am J Respir Cell Mol Biol
Pays: United States
ID NLM: 8917225
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
pubmed:
13
2
2020
medline:
21
10
2020
entrez:
13
2
2020
Statut:
ppublish
Résumé
Decreased angiogenesis contributes to persistent pulmonary hypertension of the newborn (PPHN); mechanisms remain unclear. AMPK (5'AMP activated protein kinase) is a key regulator of cell metabolism. We investigated the hypothesis that a decrease in AMPK function leads to mitochondrial dysfunction and altered balance of notch ligands delta-like 4 (DLL4) and Jagged 1 (Jag1) to impair angiogenesis in PPHN. Studies were done in fetal lambs with PPHN induced by prenatal ductus arteriosus constriction and gestation-matched control lambs. PPHN lambs were treated with saline or AMPK agonist metformin. Angiogenesis was assessed in lungs with micro-computed tomography angiography and histology. AMPK function; expression of mitochondrial electron transport chain (ETC) complex proteins I-V, Dll4, and Jag1; mitochondrial number; and
Identifiants
pubmed: 32048878
doi: 10.1165/rcmb.2019-0275OC
pmc: PMC7258820
doi:
Substances chimiques
Biphenyl Compounds
0
Intracellular Signaling Peptides and Proteins
0
Jagged-1 Protein
0
Ligands
0
Membrane Proteins
0
Pyrones
0
Receptors, Notch
0
Thiophenes
0
delta protein
0
Threonine
2ZD004190S
Metformin
9100L32L2N
Protein Kinases
EC 2.7.-
AMP-Activated Protein Kinase Kinases
EC 2.7.11.3
4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile
P68477CD2C
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
719-731Subventions
Organisme : NCI NIH HHS
ID : R01 CA193343
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136597
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144519
Pays : United States
Références
Arterioscler Thromb Vasc Biol. 2011 Sep;31(9):2000-6
pubmed: 21680900
Am J Respir Crit Care Med. 2007 Dec 1;176(11):1146-53
pubmed: 17823355
Am J Physiol Lung Cell Mol Physiol. 2013 Jan 1;304(1):L29-42
pubmed: 23103561
Med Sci Monit Basic Res. 2016 Mar 09;22:27-33
pubmed: 26978596
Am J Physiol Heart Circ Physiol. 2007 Apr;292(4):H1812-20
pubmed: 17142346
Drugs. 2005;65(3):385-411
pubmed: 15669880
Am J Physiol Lung Cell Mol Physiol. 2016 Jan 1;310(1):L40-9
pubmed: 26519208
Shock. 2019 Nov;52(5):540-549
pubmed: 30562237
Biochem Biophys Res Commun. 2019 Jan 29;509(1):24-31
pubmed: 30573360
Am J Physiol Lung Cell Mol Physiol. 2015 Nov 1;309(9):L1009-17
pubmed: 26320159
Dev Dyn. 2002 Jun;224(2):144-53
pubmed: 12112468
J Biol Chem. 2007 Nov 9;282(45):32539-48
pubmed: 17728241
Cell Metab. 2006 Jun;3(6):403-16
pubmed: 16753576
Science. 2005 Dec 9;310(5754):1642-6
pubmed: 16308421
J Pediatr. 1976 Oct;89(4):626-30
pubmed: 784932
Am J Physiol Lung Cell Mol Physiol. 2011 Sep;301(3):L334-45
pubmed: 21622842
Cell. 2011 Sep 16;146(6):873-87
pubmed: 21925313
Am J Physiol Lung Cell Mol Physiol. 2009 Jul;297(1):L184-95
pubmed: 19429773
Sci Rep. 2014 Feb 07;4:4031
pubmed: 24504253
J Clin Invest. 1989 Jun;83(6):1849-58
pubmed: 2723062
Cancer Sci. 2018 May;109(5):1382-1392
pubmed: 29601127
Circulation. 2016 Feb 23;133(8):717-31
pubmed: 26813102
Nat Cell Biol. 2017 Aug;19(8):915-927
pubmed: 28714968
Circ Res. 2016 Jul 8;119(2):197-209
pubmed: 27217398
Am J Physiol Lung Cell Mol Physiol. 2008 Oct;295(4):L680-7
pubmed: 18621906
Am J Physiol. 1989 Aug;257(2 Pt 2):H626-34
pubmed: 2764143
J Pediatr. 1976 Apr;88(4 Pt 1):614-20
pubmed: 1255323
Am J Physiol Heart Circ Physiol. 2003 Jul;285(1):H204-11
pubmed: 12663260
Trends Endocrinol Metab. 2012 Sep;23(9):459-66
pubmed: 22817841
Curr Opin Cell Biol. 2017 Apr;45:31-37
pubmed: 28232179
Annu Rev Physiol. 2017 Feb 10;79:43-66
pubmed: 27992732
Dev Biol. 2003 Dec 15;264(2):443-55
pubmed: 14651929
Am J Respir Crit Care Med. 2010 Feb 15;181(4):394-418
pubmed: 20130146
Am J Physiol Lung Cell Mol Physiol. 2005 Apr;288(4):L648-54
pubmed: 15579625
Physiol Rep. 2019 Feb;7(3):e13986
pubmed: 30706701
Circulation. 2008 Jul 8;118(2):157-65
pubmed: 18591437
Mol Cell Biol. 2000 Sep;20(18):6704-11
pubmed: 10958668
Angiogenesis. 2016 Apr;19(2):217-28
pubmed: 26951478