Matches in SemOpenAlex for { <https://semopenalex.org/work/W2000464736> ?p ?o ?g. }
- W2000464736 endingPage "850" @default.
- W2000464736 startingPage "839" @default.
- W2000464736 abstract "Background and purpose: Clinical indications for erythropoietin (EPO) in the vascular system reach far beyond the treatment of anemia, but the development of EPO as a non-toxic agent rests heavily upon the cellular pathways controlled by EPO that require elucidation. Experimental approach: We modulated gene activity and examined cellular trafficking of critical pathways during oxidative stress that may work in concert with EPO to protect primary cerebral endothelial cells (ECs) during oxidative stress, namely protein kinase B (Akt1), 14-3-3 protein, the Forkhead transcription factor FOXO3a. Key results: Here, we show that preservation of ECs by EPO during oxygen-glucose deprivation (OGD) required the initial activation of the phosphatidylinositol 3-kinase (PI-3K) pathway through Akt1, since specific pharmacological blockade of Akt1 activity or gene silencing of Akt1 prevented EC protection by EPO. EPO subsequently involved a series of anti-apoptotic pathways to activate STAT3, STAT5, and ERK 1/2. Furthermore, EPO maintained the inhibitory phosphorylation and integrity of the ‘pro-apoptotic’ transcription factor FOXO3a, promoted the binding of FOXO3a to 14-3-3 protein and regulated the intracellular trafficking of FOXO3a. Additionally, gene silencing of FOXO3a during OGD significantly increased EC survival, but did not synergistically improve cytoprotection by EPO, illustrating that EPO relied upon the blockade of the FOXO3a pathway. Conclusions and implications: Our work defines a novel cytoprotective pathway in ECs that involves PI-3 K, STAT3, STAT5, ERK 1/2, 14-3-3 protein and FOXO3a, which can be targeted for the development of EPO as a clinically effective and safe agent in the vascular system. British Journal of Pharmacology (2007) 150, 839–850. doi:10.1038/sj.bjp.0707161" @default.
- W2000464736 created "2016-06-24" @default.
- W2000464736 creator A5000415542 @default.
- W2000464736 creator A5057464586 @default.
- W2000464736 date "2007-04-01" @default.
- W2000464736 modified "2023-10-18" @default.
- W2000464736 title "Erythropoietin involves the phosphatidylinositol 3-kinase pathway, 14-3-3 protein and FOXO3a nuclear trafficking to preserve endothelial cell integrity" @default.
- W2000464736 cites W1547877665 @default.
- W2000464736 cites W1907048502 @default.
- W2000464736 cites W1974811729 @default.
- W2000464736 cites W1980232013 @default.
- W2000464736 cites W1981955192 @default.
- W2000464736 cites W1990368435 @default.
- W2000464736 cites W1991500856 @default.
- W2000464736 cites W1992736496 @default.
- W2000464736 cites W1993781471 @default.
- W2000464736 cites W1993799540 @default.
- W2000464736 cites W1997611649 @default.
- W2000464736 cites W2002174333 @default.
- W2000464736 cites W2014621947 @default.
- W2000464736 cites W2017828532 @default.
- W2000464736 cites W2020562174 @default.
- W2000464736 cites W2028628328 @default.
- W2000464736 cites W2029294948 @default.
- W2000464736 cites W2032103118 @default.
- W2000464736 cites W2035496195 @default.
- W2000464736 cites W2039274105 @default.
- W2000464736 cites W2043058596 @default.
- W2000464736 cites W2045212640 @default.
- W2000464736 cites W2048620881 @default.
- W2000464736 cites W2054992202 @default.
- W2000464736 cites W2058316500 @default.
- W2000464736 cites W2061781939 @default.
- W2000464736 cites W2066914106 @default.
- W2000464736 cites W2068423530 @default.
- W2000464736 cites W2071719170 @default.
- W2000464736 cites W2079387700 @default.
- W2000464736 cites W2082665949 @default.
- W2000464736 cites W2085029073 @default.
- W2000464736 cites W2086437884 @default.
- W2000464736 cites W2096260067 @default.
- W2000464736 cites W2105435289 @default.
- W2000464736 cites W2108689485 @default.
- W2000464736 cites W2108712459 @default.
- W2000464736 cites W2109674240 @default.
- W2000464736 cites W2111762687 @default.
- W2000464736 cites W2114496904 @default.
- W2000464736 cites W2116216629 @default.
- W2000464736 cites W2117688788 @default.
- W2000464736 cites W2122817227 @default.
- W2000464736 cites W2125369648 @default.
- W2000464736 cites W2133203383 @default.
- W2000464736 cites W2158030857 @default.
- W2000464736 cites W2161182825 @default.
- W2000464736 cites W2161282966 @default.
- W2000464736 cites W2162434225 @default.
- W2000464736 cites W2162885883 @default.
- W2000464736 cites W2166403721 @default.
- W2000464736 cites W2166941736 @default.
- W2000464736 cites W2168946139 @default.
- W2000464736 cites W2171768996 @default.
- W2000464736 cites W2313524961 @default.
- W2000464736 cites W2465298555 @default.
- W2000464736 doi "https://doi.org/10.1038/sj.bjp.0707161" @default.
- W2000464736 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1952181" @default.
- W2000464736 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17339844" @default.
- W2000464736 hasPublicationYear "2007" @default.
- W2000464736 type Work @default.
- W2000464736 sameAs 2000464736 @default.
- W2000464736 citedByCount "113" @default.
- W2000464736 countsByYear W20004647362012 @default.
- W2000464736 countsByYear W20004647362013 @default.
- W2000464736 countsByYear W20004647362014 @default.
- W2000464736 countsByYear W20004647362015 @default.
- W2000464736 countsByYear W20004647362016 @default.
- W2000464736 countsByYear W20004647362017 @default.
- W2000464736 countsByYear W20004647362018 @default.
- W2000464736 countsByYear W20004647362019 @default.
- W2000464736 countsByYear W20004647362020 @default.
- W2000464736 countsByYear W20004647362021 @default.
- W2000464736 countsByYear W20004647362022 @default.
- W2000464736 countsByYear W20004647362023 @default.
- W2000464736 crossrefType "journal-article" @default.
- W2000464736 hasAuthorship W2000464736A5000415542 @default.
- W2000464736 hasAuthorship W2000464736A5057464586 @default.
- W2000464736 hasBestOaLocation W20004647361 @default.
- W2000464736 hasConcept C104317684 @default.
- W2000464736 hasConcept C119056186 @default.
- W2000464736 hasConcept C134018914 @default.
- W2000464736 hasConcept C184235292 @default.
- W2000464736 hasConcept C2776151105 @default.
- W2000464736 hasConcept C2778534260 @default.
- W2000464736 hasConcept C2778923194 @default.
- W2000464736 hasConcept C2779391668 @default.
- W2000464736 hasConcept C2780967304 @default.
- W2000464736 hasConcept C55493867 @default.
- W2000464736 hasConcept C57074206 @default.
- W2000464736 hasConcept C62478195 @default.