title: Protein repertoire impact of Ubiquitin-Proteasome System impairment: insight into the protective role of beta-estradiol.
abstract: The Ubiquitin-Proteasome System (UPS) and the Autophagy-Lysosome Pathways (ALP) are key mechanisms for cellular homeostasis sustenance and protein clearance. A wide number of Neurodegenerative Diseases (NDs) are tied with UPS impairment and have been also described as proteinopathies caused by aggregate-prone proteins, not efficiently removed by proteasome. Despite the large knowledge on proteasome biological role, molecular mechanisms associated with its impairment are still blur. We have pursued a comprehensive proteomic investigation to evaluate the phenotypic rearrangements in protein repertoires associated with a UPS blockage. Different functional proteomic approaches have been employed to tackle UPS impairment impact on human NeuroBlastoma (NB) cell lines responsive to proteasome inhibition by Epoxomicin. 2-Dimensional Electrophoresis (2-DE) separation combined with Mass Spectrometry and Shotgun Proteomics experiments have been employed to design a thorough picture of protein profile. Unsupervised meta-analysis of the collected proteomic data revealed that all the identified proteins relate each other in a functional network centered on beta-estradiol. Moreover we showed that treatment of cells with beta-estradiol resulted in aggregate removal and increased cell survival due to activation of the autophagic pathway. Our data may provide the molecular basis for the use of beta-estradiol in neurodegenerative disorders by induction of protein aggregate removal.
authors.affiliation: Department of Internal Medicine, University of Rome Tor Vergata, Faculty of Medicine and Surgery, Via Montpellier, 1, 00133-Rome, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: D'Alessandro
authors.forename: Simona
authors.initials: S
authors.lastname: D'Aguanno
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Cencioni
authors.forename: Luisa
authors.initials: L
authors.lastname: Pieroni
authors.forename: Adamo
authors.initials: A
authors.lastname: Diamantini
authors.forename: Luca
authors.initials: L
authors.lastname: Battistini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Longone
authors.forename: Alida
authors.initials: A
authors.lastname: Spalloni
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Laurenzi
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
mesh_terms: D001343:Autophagy; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004958:Estradiol / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D008954:Models, Biological; D009447:Neuroblastoma / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D004958:Estradiol; D046988:Proteasome Endopeptidase Complex