title: Lifelong maintenance of composition, function and cellular/subcellular distribution of proteasomes in human liver.
abstract: Owing to organ shortage, livers from old donors are increasingly used for transplantation. The function and duration of such transplanted livers are apparently comparable to those from young donors, suggesting that, despite some morphological and structural age-related changes, no major functional changes do occur in liver with age. We tested this hypothesis by performing a comprehensive study on proteasomes, major cell organelles responsible for proteostasis, in liver biopsies from heart-beating donors. Oxidized and poly-ubiquitin conjugated proteins did not accumulate with age and the three major proteasome proteolytic activities were similar in livers from young and old donors. Analysis of proteasomes composition showed an age-related increased of β5i/α4 ratio, suggesting a shift toward proteasomes containing inducible subunits and a decreased content of PA28α subunit, mainly in the cytosol of hepatocytes. Thus our data suggest that, proteasomes activity is well preserved in livers from aged donors, concomitantly with subtle changes in proteasome subunit composition which might reflect the occurrence of a functional remodelling to maintain an efficient proteostasis. Gender differences are emerging and they deserve further investigations owing to the different aging trajectories between men and women. Finally, our data support the safe use of livers from old donors for transplantation.
authors.affiliation: Interdepartmental Centre "L. Galvani" for Integrated Studies on Biophysics, Bioinformatics and Biocomplexity (CIG), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy. Electronic address: elena.bellavista2@unibo.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Bellavista
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy. Electronic address: morena.martucci3@unibo.it.
authors.forename: Morena
authors.initials: M
authors.lastname: Martucci
authors.affiliation: "F. Addarii" Institute of Oncology and Transplant Pathology at Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, 40138 Bologna, Italy. Electronic address: francesco.vasuri@aosp.bo.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Vasuri
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy. Electronic address: aurelia.santoro@unibo.it.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Institute of Biochemistry, Charité Universitaetsmedizin Berlin, 10117 Berlin, Germany; Centro Interdipartimentale di Ricerca sul Cancro "Giorgio Prodi" (CIRC), University of Bologna, 40126 Bologna, Italy. Electronic address: michele.mishto@charite.de.
authors.forename: Michele
authors.initials: M
authors.lastname: Mishto
authors.affiliation: Institute of Biochemistry, Charité Universitaetsmedizin Berlin, 10117 Berlin, Germany. Electronic address: alex.kloss@charite.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kloss
authors.affiliation: "F. Addarii" Institute of Oncology and Transplant Pathology at Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, 40138 Bologna, Italy. Electronic address: elisa.capizzi@libero.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Capizzi
authors.affiliation: "F. Addarii" Institute of Oncology and Transplant Pathology at Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, 40138 Bologna, Italy. Electronic address: alessio.degiovanni@gmail.com.
authors.forename: Alessio
authors.initials: A
authors.lastname: Degiovanni
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy. Electronic address: catia.lanzarini2@unibo.it.
authors.forename: Catia
authors.initials: C
authors.lastname: Lanzarini
authors.affiliation: Interdepartmental Centre "L. Galvani" for Integrated Studies on Biophysics, Bioinformatics and Biocomplexity (CIG), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; Department of Physics and Astronomy (DIFA) and INFN Sez. Bologna, Alma Mater Studiorum, University of Bologna, 40127 Bologna, Italy. Electronic address: daniel.remondini@unibo.it.
authors.forename: Daniel
authors.initials: D
authors.lastname: Remondini
authors.affiliation: Department of General Surgery and Organ Transplantation, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy. Electronic address: alled78@yahoo.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Dazzi
authors.affiliation: Department of General Surgery and Organ Transplantation, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy. Electronic address: sarapellegrini@hotmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Pellegrini
authors.affiliation: Department of General Surgery and Organ Transplantation, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy. Electronic address: matteo.cescon@aosp.bo.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cescon
authors.affiliation: Interdepartmental Centre "L. Galvani" for Integrated Studies on Biophysics, Bioinformatics and Biocomplexity (CIG), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy. Electronic address: miriam.capri@unibo.it.
authors.forename: Miriam
authors.initials: M
authors.lastname: Capri
authors.affiliation: Interdepartmental Centre "L. Galvani" for Integrated Studies on Biophysics, Bioinformatics and Biocomplexity (CIG), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy. Electronic address: stefano.salvioli@unibo.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Salvioli
authors.affiliation: "F. Addarii" Institute of Oncology and Transplant Pathology at Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, 40138 Bologna, Italy. Electronic address: derrico@aosp.bo.it.
authors.forename: Antonia
authors.initials: A
authors.lastname: D'Errico-Grigioni
authors.affiliation: Institute of Biochemistry, Charité Universitaetsmedizin Berlin, 10117 Berlin, Germany. Electronic address: burkhardt.dahlmann@charite.de.
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Dahlmann
authors.affiliation: Istituto Nazionale Tumori Regina Elena, 00144 Roma, Italy. Electronic address: grazi@ifo.it.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Grazi
authors.affiliation: Interdepartmental Centre "L. Galvani" for Integrated Studies on Biophysics, Bioinformatics and Biocomplexity (CIG), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; IRCCS Institute of Neurological Sciences, 40139 Bologna, Italy; National Research Council of Italy, CNR, Institute for Organic Synthesis and Photoreactivity (ISOF), 40129 Bologna, Italy; National Research Council of Italy, CNR, Institute of Molecular Genetics, Unit of Bologna IOR, 40136 Italy. Electronic address: claudio.franceschi@unibo.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D012727:Sex Characteristics
chemical_list: D046988:Proteasome Endopeptidase Complex
keywords: Aging; Gender; Human liver; Immunoproteasome; PA28αβ regulator; Standard proteasome