The role of phosphoglycerate dehydrogenase (PHGDH), a key enzyme of the serine synthesis pathway (SSP), in endothelial cells (ECs) remains poorly characterized. We report that mouse neonates with EC-specific PHGDH deficiency suffer lethal vascular defects within days of gene inactivation, due to reduced EC proliferation and survival. In addition to nucleotide synthesis impairment, PHGDH knockdown (PHGDHKD) caused oxidative stress, due not only to decreased glutathione and NADPH synthesis but also to mitochondrial dysfunction. Electron transport chain (ETC) enzyme activities were compromised upon PHGDHKD because of insufficient heme production due to cellular serine depletion, not observed in other cell types. As a result of heme depletion, elevated reactive oxygen species levels caused EC demise. Supplementation of hemin in PHGDHKD ECs restored ETC function and rescued the apoptosis and angiogenesis defects. These data argue that ECs die upon PHGDH inhibition, even without external serine deprivation, illustrating an unusual importance of serine synthesis for ECs.
Pubmed ID: 30017355 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsInternational functional genomics data collection generated from microarray or next-generation sequencing (NGS) platforms. Repository of functional genomics data supporting publications. Provides genes expression data for reuse to the research community where they can be queried and downloaded. Integrated with the Gene Expression Atlas and the sequence databases at the European Bioinformatics Institute. Contains a subset of curated and re-annotated Archive data which can be queried for individual gene expression under different biological conditions across experiments. Data collected to MIAME and MINSEQE standards. Data are submitted by users or are imported directly from the NCBI Gene Expression Omnibus.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsThis monoclonal targets Parkin (Prk8)
View all literature mentionsThis polyclonal targets alpha-Tubulin
View all literature mentionsThis polyclonal secondary targets Mouse IgG (H+L)
View all literature mentionsThis monoclonal targets AMPK-alpha, phospho (Thr172)
View all literature mentionsThis unknown targets
View all literature mentionsThis unknown targets Goat IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets Green Fluorescent Protein (GFP)
View all literature mentionsThis monoclonal targets Actin alpha-Smooth Muscle - Cy3(TM) antibody produced in mouse
View all literature mentionsThis monoclonal targets Human DHODH
View all literature mentionsThis monoclonal targets p21 Waf1/Cip1
View all literature mentionsThis monoclonal targets PGC-1alpha (3G6) Rabbit mAb
View all literature mentionsThis monoclonal targets TOMM20 antibody
View all literature mentionsThis recombinant monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets Mouse Endoglin/CD105 Affinity Purified Ab
View all literature mentionsThis monoclonal targets CD31 (PECAM-1)
View all literature mentionsThis monoclonal targets CD31 (PECAM-1)
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis unknown targets OXPHOS
View all literature mentionsThis monoclonal targets AMPK (D63G4)
View all literature mentionsThis unknown targets Human PHGDH
View all literature mentionsThis polyclonal targets NG2 Chondroitin Sulfate Proteoglycan
View all literature mentionsThis monoclonal targets human Annexin V
View all literature mentionsThis monoclonal targets AMPK-alpha, phospho (Thr172)
View all literature mentionsThis polyclonal targets alpha-Tubulin
View all literature mentionsThis monoclonal targets Parkin (Prk8)
View all literature mentionsThis polyclonal secondary targets Mouse IgG (H+L)
View all literature mentions