2017
Macrophage deficiency of miR‐21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis
Canfrán‐Duque A, Rotllan N, Zhang X, Fernández‐Fuertes M, Ramírez‐Hidalgo C, Araldi E, Daimiel L, Busto R, Fernández‐Hernando C, Suárez Y. Macrophage deficiency of miR‐21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis. EMBO Molecular Medicine 2017, 9: 1244-1262. PMID: 28674080, PMCID: PMC5582411, DOI: 10.15252/emmm.201607492.Peer-Reviewed Original ResearchConceptsER stress-induced apoptosisPost-translational degradationFoam cell formationMiR-21MiR-21 target genesTarget genesJNK signalingPlaque necrosisAbundant miRNAVascular inflammationAccumulation of lipidsHematopoietic cellsMacrophage apoptosisCell formationAberrant expressionMacrophage deficiencyApoptosisCholesterol effluxProgression of atherosclerosisChronic inflammatory diseasePathophysiological processesInflammatory cellsExpressionInflammatory diseasesCardiovascular disease
2016
ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression
Aryal B, Rotllan N, Araldi E, Ramírez CM, He S, Chousterman BG, Fenn AM, Wanschel A, Madrigal-Matute J, Warrier N, Martín-Ventura JL, Swirski FK, Suárez Y, Fernández-Hernando C. ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression. Nature Communications 2016, 7: 12313. PMID: 27460411, PMCID: PMC4974469, DOI: 10.1038/ncomms12313.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-Like Protein 4AnimalsApoptosisAtherosclerosisBone Marrow TransplantationCell ProliferationCell SurvivalDisease ProgressionFoam CellsHematopoietic Stem CellsHumansInflammationLeukocytosisMacrophagesMaleMiceMice, Inbred C57BLModels, BiologicalMonocytesMyeloid Progenitor CellsPlaque, AtheroscleroticConceptsFoam cell formationMyeloid progenitor cell expansionANGPTL4 deficiencyCell formationMacrophage gene expressionLipid raft contentMyeloid progenitor populationsProgenitor cell expansionUpregulated genesProgenitor populationsGene expressionHaematopoietic cellsCell surfaceMacrophage apoptosisCell expansionCells resultsProtein 4Lipid accumulationCD36 expressionLike protein 4ExpressionProfound effectMacrophagesGenesLarger atherosclerotic plaques
2007
Loss of Akt1 Leads to Severe Atherosclerosis and Occlusive Coronary Artery Disease
Fernández-Hernando C, Ackah E, Yu J, Suárez Y, Murata T, Iwakiri Y, Prendergast J, Miao RQ, Birnbaum MJ, Sessa WC. Loss of Akt1 Leads to Severe Atherosclerosis and Occlusive Coronary Artery Disease. Cell Metabolism 2007, 6: 446-457. PMID: 18054314, PMCID: PMC3621848, DOI: 10.1016/j.cmet.2007.10.007.Peer-Reviewed Original ResearchMeSH KeywordsAcute Coronary SyndromeAnimalsApolipoproteins EApoptosisAtherosclerosisBone Marrow TransplantationCoronary OcclusionDisease Models, AnimalEndothelial CellsFemaleHumansInflammation MediatorsMacrophagesMaleMiceMice, KnockoutNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIProto-Oncogene Proteins c-aktConceptsLoss of Akt1Apolipoprotein E knockout backgroundOcclusive coronary artery diseaseBone marrow transfer experimentsAcute coronary syndromeCoronary artery diseaseLesion expansionCoronary syndromeCoronary atherosclerosisSevere atherosclerosisArtery diseaseInflammatory mediatorsCoronary lesionsVascular protectionVascular originProinflammatory genesENOS phosphorylationCardiovascular systemLesion formationGenetic ablationEndothelial cellsAtherogenesisEnhanced expressionKnockout backgroundVessel wall
2006
Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation
González-Santiago L, Suárez Y, Zarich N, Muñoz-Alonso M, Cuadrado A, Martínez T, Goya L, Iradi A, Sáez-Tormo G, Maier J, Moorthy A, Cato A, Rojas J, Muñoz A. Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation. Cell Death & Differentiation 2006, 13: 1968-1981. PMID: 16543941, DOI: 10.1038/sj.cdd.4401898.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisBreast NeoplasmsCalciumCell Cycle ProteinsCopperDepsipeptidesDown-RegulationDual Specificity Phosphatase 1Enzyme ActivationGlutathione DisulfideGlutathione PeroxidaseGlutathione ReductaseHeLa CellsHomeostasisHumansImmediate-Early ProteinsJNK Mitogen-Activated Protein KinasesMembrane PotentialsMiceMitochondrial MembranesOxidative StressPeptides, CyclicPhosphoprotein PhosphatasesProtein Phosphatase 1Protein Tyrosine PhosphatasesRac1 GTP-Binding ProteinReactive Oxygen SpeciesConceptsJun N-terminal kinaseJNK activationRac1 activationGlutathione homeostasisRac1 small GTPaseJNK-dependent apoptosisRac1 GTPase activationMitochondrial membrane potentialN-terminal kinaseMKP-1 phosphataseSmall GTPaseGTPase activationReactive oxygen speciesHuman breast cancer cellsGSSG/GSH ratioCell deathBreast cancer cellsRapid activationExogenous GSHRNA duplexesSustained activationGSH synthesisSpecific Rac1 inhibitorAplidinDownregulation of Rac1
2004
JNK activation is critical for Aplidin™-induced apoptosis
Cuadrado A, González L, Suárez Y, Martínez T, Muñoz A. JNK activation is critical for Aplidin™-induced apoptosis. Oncogene 2004, 23: 4673-4680. PMID: 15122339, DOI: 10.1038/sj.onc.1207636.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsApoptosisBlotting, WesternBreast NeoplasmsCell DivisionCell Line, TumorCell SurvivalDepsipeptidesEnzyme ActivationFemaleFibroblastsHumansMitogen-Activated Protein KinasesNF-kappa BPeptides, CyclicPhosphorylationPrecipitin TestsProto-Oncogene Proteins c-junTranscription Factor AP-1
2003
Kahalalide F, a new marine-derived compound, induces oncosis in human prostate and breast cancer cells.
Suárez Y, González L, Cuadrado A, Berciano M, Lafarga M, Muñoz A. Kahalalide F, a new marine-derived compound, induces oncosis in human prostate and breast cancer cells. Molecular Cancer Therapeutics 2003, 2: 863-72. PMID: 14555705.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid Chloromethyl KetonesApoptosisBreast NeoplasmsCaspase InhibitorsCaspasesCell CycleCell NucleusCell Transformation, NeoplasticCysteine Proteinase InhibitorsDepsipeptidesFemaleFlow CytometryHumansLysosomesMaleMollusk VenomsOligopeptidesPeptidesProstatic NeoplasmsTumor Cells, CulturedConceptsAnti-apoptotic Bcl-2 proteinGeneral caspase inhibitorSevere cytoplasmic swellingMitochondrial membrane potentialCell cycle arrestBcl-2 proteinKahalalide FTranslation inhibitorsMarine-derived compoundsNuclear domainsCaspase inhibitorsNuclear envelopeNew marine-derived compoundDNA degradationEndoplasmic reticulumHuman cellsCell deathNovel antitumor drugsBreast cancer cellsJC-1LysoTracker GreenCell nucleiBreast cancer cell linesCancer cell linesMitochondrial damage
2002
AplidinTM Induces Apoptosis in Human Cancer Cells via Glutathione Depletion and Sustained Activation of the Epidermal Growth Factor Receptor, Src, JNK, and p38 MAPK*
Cuadrado A, Garcı́a-Fernández L, González L, Suárez Y, Losada A, Alcaide V, Martı́nez T, Fernández-Sousa J, Sánchez-Puelles J, Muñoz A. AplidinTM Induces Apoptosis in Human Cancer Cells via Glutathione Depletion and Sustained Activation of the Epidermal Growth Factor Receptor, Src, JNK, and p38 MAPK*. Journal Of Biological Chemistry 2002, 278: 241-250. PMID: 12414812, DOI: 10.1074/jbc.m201010200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisBreast NeoplasmsCell DivisionCell SurvivalCells, CulturedDepsipeptidesEnzyme ActivationEnzyme InhibitorsErbB ReceptorsFemaleFibroblastsFlow CytometryGlutathioneHumansJNK Mitogen-Activated Protein KinasesKidney NeoplasmsMiceMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPeptides, CyclicPhosphorylationProto-Oncogene Proteins pp60(c-src)Receptors, Platelet-Derived Growth FactorTumor Cells, CulturedConceptsEpidermal growth factor receptorP38 MAPK activationP38 MAPKNon-receptor protein tyrosine kinase SrcGrowth factor receptorMAPK activationProtein tyrosine kinase SrcStress response programSustained activationFactor receptorCancer cellsMDA-MB-231 breast cancer cellsHuman cancer cellsBenzyloxycarbonyl-VADKinase SrcHuman MDA-MB-231 breast cancer cellsMDA-MB-231 cellsMolecular basisKinase JNKPretreatment of cellsMouse embryosEGFR activationFluoromethyl ketoneGrowth arrestHuman renal cancer
2001
Dose-dependent effects of lovastatin on cell cycle progression. Distinct requirement of cholesterol and non-sterol mevalonate derivatives
Martı́nez-Botas J, Ferruelo A, Suárez Y, Fernández C, Gómez-Coronado D, Lasunción M. Dose-dependent effects of lovastatin on cell cycle progression. Distinct requirement of cholesterol and non-sterol mevalonate derivatives. Biochimica Et Biophysica Acta 2001, 1532: 185-194. PMID: 11470239, DOI: 10.1016/s1388-1981(01)00125-1.Peer-Reviewed Original ResearchConceptsCell proliferationLow-density lipoprotein cholesterolCell cycle progressionDose-dependent effectCell cycle distributionCell cycleCycle progressionLipoprotein cholesterolConcentrations of lovastatinCholesterol supplyCycle distributionCholesterolLovastatinHuman cell linesCell linesCholesterol biosynthesisCholesterol-free mediumNormal cell cyclingM phaseProgressionProliferationPresent studyHL-60Mevalonate derivativesCell cycling
1998
Induction of apoptosis in p53-null HL-60 cells by inhibition of lanosterol 14-α demethylase
Martínez-Botas J, Ferruelo A, Suárez Y, Gómez-Coronado D, Lasunción M. Induction of apoptosis in p53-null HL-60 cells by inhibition of lanosterol 14-α demethylase. Biochimie 1998, 80: 887-894. PMID: 9893947, DOI: 10.1016/s0300-9084(00)88884-7.Peer-Reviewed Original Research