2024
Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage
Ruz-Maldonado I, Gonzalez J, Zhang H, Sun J, Bort A, Kabir I, Kibbey R, Suárez Y, Greif D, Fernández-Hernando C. Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage. Nature Communications 2024, 15: 1247. PMID: 38341404, PMCID: PMC10858916, DOI: 10.1038/s41467-024-45439-0.Peer-Reviewed Original Research
2019
PDE1 inhibition facilitates proteasomal degradation of misfolded proteins and protects against cardiac proteinopathy
Zhang H, Pan B, Wu P, Parajuli N, Rekhter MD, Goldberg AL, Wang X. PDE1 inhibition facilitates proteasomal degradation of misfolded proteins and protects against cardiac proteinopathy. Science Advances 2019, 5: eaaw5870. PMID: 31131329, PMCID: PMC6531002, DOI: 10.1126/sciadv.aaw5870.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-Crystallin B ChainAnimalsCyclic AMP-Dependent Protein KinasesCyclic GMP-Dependent Protein KinasesCyclic Nucleotide Phosphodiesterases, Type 1DensitometryEchocardiographyFemaleGenotypeHeart FailureHeart VentriclesHemodynamicsHumansHydrolysisMaleMiceMice, TransgenicMicroscopy, FluorescenceMyocytes, CardiacPhosphorylationProteasome Endopeptidase ComplexProtein DenaturationProtein FoldingProteostasis DeficienciesRats
2017
TFEB activation protects against cardiac proteotoxicity via increasing autophagic flux
Pan B, Zhang H, Cui T, Wang X. TFEB activation protects against cardiac proteotoxicity via increasing autophagic flux. Journal Of Molecular And Cellular Cardiology 2017, 113: 51-62. PMID: 28993153, PMCID: PMC5656243, DOI: 10.1016/j.yjmcc.2017.10.003.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-Crystallin B ChainAnimalsAutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell SurvivalFemaleHeart DiseasesHeart VentriclesLysosomesMaleMechanistic Target of Rapamycin Complex 1MiceMice, TransgenicMyocytes, CardiacRatsRats, Sprague-DawleyRNA, MessengerSignal TransductionConceptsAutophagic-lysosomal pathwayCardiac proteinopathyAutophagic fluxTFEB target genesTFEB overexpressionActivity of TFEBMRNA levelsMTORC1 activationMaster regulatorUbiquitinated proteinsDownregulation of TFEBGenetic manipulationAutophagic cargoTarget genesMolecular basisProtein aggregatesTFEB activation
2015
COP9 Signalosome Controls the Degradation of Cytosolic Misfolded Proteins and Protects Against Cardiac Proteotoxicity
Su H, Li J, Zhang H, Ma W, Wei N, Liu J, Wang X. COP9 Signalosome Controls the Degradation of Cytosolic Misfolded Proteins and Protects Against Cardiac Proteotoxicity. Circulation Research 2015, 117: 956-966. PMID: 26383969, PMCID: PMC4636927, DOI: 10.1161/circresaha.115.306783.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-Crystallin B ChainAnimalsAnimals, NewbornAutophagyCarrier ProteinsCells, CulturedCOP9 Signalosome ComplexCullin ProteinsCytosolFemaleGenotypeHeart DiseasesHeart VentriclesMaleMice, Inbred C57BLMice, KnockoutMicrotubule-Associated ProteinsMyocytes, CardiacPhenotypeProtein FoldingProteolysisRats, Sprague-DawleyRNA InterferenceSignal TransductionTime FactorsTransfectionUbiquitinationConceptsCullin-RING ligasesCSN8/CSNCOP9 signalosomeMisfolded proteinsProtein aggregatesCardiac proteotoxicitySurrogate misfolded proteinUbiquitin-proteasome systemDeneddylation activityCSN subunitsUbiquitin ligasesG missense mutationTotal ubiquitinated proteinsUbiquitinated proteinsCardiac proteinopathyProtein degradationLigasesUbiquitinationMissense mutationsProteinLC3-IIProteotoxicityReduced levelsCultured cardiomyocytesHypomorphismPriming the proteasome by protein kinase G: a novel cardioprotective mechanism of sildenafil
Zhang H, Wang X. Priming the proteasome by protein kinase G: a novel cardioprotective mechanism of sildenafil. Future Cardiology 2015, 11: 177-189. PMID: 25760877, PMCID: PMC4370174, DOI: 10.2217/fca.15.3.Peer-Reviewed Original ResearchConceptsProtein kinase GProtein quality controlMost cellular proteinsKinase GNovel cardioprotective mechanismProteasome enhancementCardiac protein quality controlProtein kinase G activationMisfolded proteinsProtein hemostasisCellular proteinsProteasomal degradationCardiac proteinopathyHuman failing heartsProteinProteasomeNew therapeutic strategiesG activationTherapeutic strategiesMajor pathogenic factorFunctional insufficiencyCardioprotective mechanismsLarge subsetDegradationMechanism