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

详细信息    查看全文

• 作者：Annamaria D'Alessandro^a ; ^b ; Simona D'Aguanno^a ; ^b ; Maria Teresa Cencioni^b ; Luisa Pieroni^a ; ^b ; Adamo Diamantini^b ; Luca Battistini^b ; Patrizia Longone^b ; Alida Spalloni^b ; Vincenzo De Laurenzi^c ; Sergio Bernardini^a ; Giorgio Federici^a ; ^d ; Andrea Urbani^a ; ^b ; ^{andrea.urbani@uniroma2.it}
• 关键词：2-DE ; 2-Dimensional Electrophoresis ; 7-ADD ; 7-Amino-actinomycin ; ALP ; Autophagy&ndash ; Lysosome Pathways ; ALS ; Amyotrophic Lateral Sclerosis ; AV ; Annexin V ; BEH ; Bridged Ethyl Hybrid ; CMA ; Chaperone-Mediated Autophagy ; ECL ; Enhanced ChemiLuminescence ; EMRT
• 刊名：Journal of Proteomics
• 出版年：2012
• 出版时间：2 February 2012
• 年：2012
• 卷：75
• 期：4
• 页码：1440-1453
• 全文大小：1711 K

文摘

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.