2023
TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes
Boutagy N, Fowler J, Grabinska K, Cardone R, Sun Q, Vazquez K, Whalen M, Zhu X, Chakraborty R, Martin K, Simons M, Romanoski C, Kibbey R, Sessa W. TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2218150120. PMID: 37695914, PMCID: PMC10515159, DOI: 10.1073/pnas.2218150120.Peer-Reviewed Original ResearchMeSH KeywordsAcetyl Coenzyme ACytokinesEndothelial CellsHistonesHumansProtease LaTumor Necrosis Factor-alphaConceptsPyruvate dehydrogenase kinase 4Dehydrogenase kinase 4Lon proteasePyruvate dehydrogenase activityHistone acetylationMitochondrial metabolismKinase 4Specific gene lociPDH fluxEndothelial cellsSiRNA-mediated knockdownAcetyl-CoA generationLysine 27Gene transcriptionTCA fluxRNA sequencingHuman umbilical vein endothelial cellsProtein degradationHistone 3Gene locusUmbilical vein endothelial cellsNF-κB-dependent mechanismTricarboxylic acid cycle fluxVein endothelial cellsActive subunitSREBP2 regulates the endothelial response to cytokines via direct transcriptional activation of KLF6
Fowler J, Boutagy N, Zhang R, Horikami D, Whalen M, Romanoski C, Sessa W. SREBP2 regulates the endothelial response to cytokines via direct transcriptional activation of KLF6. Journal Of Lipid Research 2023, 64: 100411. PMID: 37437844, PMCID: PMC10407908, DOI: 10.1016/j.jlr.2023.100411.Peer-Reviewed Original ResearchConceptsDirect transcriptional activationTranscriptional activationEndothelial cellsChemokine expressionChromatin immunoprecipitation sequencingCholesterol homeostasisSterol-responsive genesPro-inflammatory chemokinesLipid-lowering drugsAdaptive immune responsesPro-inflammatory genesTranscription factor SREBP2Endogenous cholesterol synthesisImmunoprecipitation sequencingResponsive genesMechanism of actionPromoter regionCardiovascular riskAtherosclerotic diseaseInflammatory phenotypeImmune modulationCardiovascular diseaseImmune responseInflammatory stimuliI interferon
1998
Hypotension and inflammatory cytokine gene expression triggered by factor Xa–nitric oxide signaling
Papapetropoulos A, Piccardoni P, Cirino G, Bucci M, Sorrentino R, Cicala C, Johnson K, Zachariou V, Sessa W, Altieri D. Hypotension and inflammatory cytokine gene expression triggered by factor Xa–nitric oxide signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 4738-4742. PMID: 9539808, PMCID: PMC22560, DOI: 10.1073/pnas.95.8.4738.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCytokinesEndothelium, VascularFactor XaFibrinogenGene Expression RegulationHistamineHumansHypotensionInflammationInterleukin-6MaleNG-Nitroarginine Methyl EsterNitric OxidePolymerase Chain ReactionRatsRats, WistarSplanchnic CirculationStereoisomerismTumor Necrosis Factor-alphaUmbilical VeinsConceptsEffector cell protease receptor-1Cytokine gene expressionFactor XaReceptor 1NO synthase inhibitor LNitric oxideInflammatory cytokine gene expressionActivation of coagulationNitroarginine methyl esterEndothelial cell releaseTissue factor pathway inhibitorAcute phase responseEndothelial cell ligandsThrombin inhibitor hirudinInterleukin-6 mRNAFactor pathway inhibitorDose-dependent mannerVascular endothelial cellsL-NAMED-NAMEGrowth factor peptidesInterleukin-6Dose-dependent reactionCell ligandsPathway inhibitor