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