Galano, Eugenio (2013) DEVELOPING AN INTEGRATED OMICS TECHNOLOGY TO ELUCIDATE BIOLOGICAL MECHANIISM OF METAL EXPOSURE. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: DEVELOPING AN INTEGRATED OMICS TECHNOLOGY TO ELUCIDATE BIOLOGICAL MECHANIISM OF METAL EXPOSURE
Creators:
CreatorsEmail
Galano, Eugenioeugenio.galano@unina.it
Date: 14 March 2013
Number of Pages: 200
Institution: Università degli Studi di Napoli Federico II
Department: Scienze Chimiche
Scuola di dottorato: Biotecnologie
Dottorato: Scienze biotecnologiche
Ciclo di dottorato: 25
Coordinatore del Corso di dottorato:
nomeemail
Sannia, Giovannisannia@unina.it
Tutor:
nomeemail
Amoresano, Angelaangela.amoresano@unina.it
Date: 14 March 2013
Number of Pages: 200
Uncontrolled Keywords: Metalloproteomica, Cambiamenti del proteoma in seguito a esposizione a metalli
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/10 - Biochimica
Area 03 - Scienze chimiche > CHIM/01 - Chimica analitica
Date Deposited: 03 Apr 2013 14:28
Last Modified: 23 Jul 2014 09:37
URI: http://www.fedoa.unina.it/id/eprint/9107
DOI: 10.6092/UNINA/FEDOA/9107

Abstract

About 30% of all annotated proteins reported in the major databases (PDB, NCBInr,and Uniprot) results to be associated with a metal. In some cases the functions of these proteins strongly depend by the interaction with the right metal. Metal ions, associated with macromolecules, are utilized by biological systems in fundamental processes; therefore cytosolic concentrations of metals are tightly controlled. For a complete characterization of cell chemistry, the understanding of mechanisms by which a metal is sensed, stored, or incorporated as a cofactor is required. Some metals, such as Ca, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni and Zn, are essential,in fact they serve as micronutrients and are used for redox-processes, to stabilize molecules through electrostatic interactions, as components of various enzymes and for regulation of osmotic pressure. Many other metals, in particular heavy metals, have no biological role (e.g. Ag, Al, Cd, Au, Pb and Hg), and are nonessential and potentially toxic to mammalians and microorganisms. Selenium is a crucial micronutrient for human health. In human Se is a component of several important selenoproteins and enzymes required for different functions, such as antioxidant defense and reduction of inflammation. Several organisms possess the ability to metabolize Se into protein by a specific pathway dedicated to the biosynthesis of proteins which contain the aminoacid selenocysteine (Sec, U), or by a non-specific mechanism. The improvements in high-throughput technology, has led to born of a large number of new “omics” disciplines with the aim to expand the knowledge acquired. Thus “metallomics” was born; this term, coined by Haraguchi, denotes the ensemble of research activities related to metals of biological interest. However detailed knowledge of interaction between metals and proteins within organisms is fundamental to prevent diseases related to heavy metals pollutions, or to use some detoxification process to produce more bio-available forms of selenocontaining compounds. This PhD thesis targeted the characterization of metals involved in relevant biological processes by metallomics and proteomics approaches. Thus the following systems of biotechnological interest have been analyzed in this study: 1) Escherichia coli used as model organism for a study of the effects of heavy-metals contamination. The development of an integrated metallomics-proteomics approach for the investigation of the effects of cadmium exposure on Escherichia coli is reported. 2) HRCE (Human Renal Cortical Epithelial) cells for an investigation of the effects to cadmium and lead exposure. Apoptotic pathway was demonstrated to be induced by either cadmium or lead, with the latter the more toxic for human primary renal cells. 3) Lactobacillus reuteri Lb2 BM-DSM 16143 to study the incorporation of selenium into selenocysteines by an integrated ICP-MS based approach. Characterization of the ability of this probiotic microorganism to recover high concentration of selenium and convert them into selenocysteines residues, within the primary sequence of some proteins, is reported, representing an additional innovative approach to solve human selenium deficiency.

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