Protein repertoire impact of Ubiquitin-Proteasome System impairment: Insight into the protective role of beta-estradiol

Annamaria D'Alessandro, Simona D'Aguanno, Maria Teresa Cencioni, Luisa Pieroni, Adamo Diamantini, Luca Battistini, Patrizia Longone, Alida Spalloni, Vincenzo De Laurenzi, Sergio Bernardini, Giorgio Federici, Andrea Urbani

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1440-1453
Number of pages14
JournalJournal of Proteomics
Volume75
Issue number4
DOIs
Publication statusPublished - Feb 2 2012

Keywords

  • 2-Dimensional Electrophoresis separation
  • Beta-Estradiol
  • Meta-analysis
  • Neurodegenerative Diseases
  • Shotgun Proteomics
  • Ubiquitin-Proteasome System impairment

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

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