Lifelong maintenance of composition, function and cellular/subcellular distribution of proteasomes in human liver
Autor: | Francesco Vasuri, Alessio Degiovanni, Alexander Kloss, Daniel Remondini, Stefano Salvioli, Morena Martucci, Elisa Capizzi, Alessandro Dazzi, Michele Mishto, Gian Luca Grazi, Matteo Cescon, Antonia D’Errico-Grigioni, Claudio Franceschi, Burkhardt Dahlmann, S. Pellegrini, Catia Lanzarini, Elena Bellavista, Miriam Capri, Aurelia Santoro |
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Přispěvatelé: | Bellavista, Elena, Martucci, Morena, Vasuri, Francesco, Santoro, Aurelia, Mishto, Michele, Kloss, Alexander, Capizzi, Elisa, Degiovanni, Alessio, Lanzarini, Catia, Remondini, Daniel, Dazzi, Alessandro, Pellegrini, Sara, Cescon, Matteo, Capri, Miriam, Salvioli, Stefano, D'Errico-Grigioni, Antonia, Dahlmann, Burkhardt, Grazi, Gian Luca, Franceschi, Claudio |
Rok vydání: | 2014 |
Předmět: |
Adult
Male Aging Proteasome Endopeptidase Complex Adolescent Proteolysis Protein subunit Biology Immunoproteasome Organelle medicine Humans Proteolysi PA28αβ regulator Sex Characteristics medicine.diagnostic_test Medicine (all) Gender Sex Characteristic Middle Aged Cell biology Transplantation Human liver Cytosol Ageing Proteostasis Proteasome Biochemistry Liver Female Standard proteasome Function (biology) Human Developmental Biology |
Zdroj: | Mechanisms of ageing and development. |
ISSN: | 1872-6216 |
Popis: | 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. 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. |
Databáze: | OpenAIRE |
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