Studies on immunoproteasome in human liver. Part I: Absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis

Francesco Vasuri, Elisa Capizzi, Elena Bellavista, Michele Mishto, Aurelia Santoro, Michelangelo Fiorentino, Miriam Capri, Matteo Cescon, Gian Luca Grazi, Walter Franco Grigioni, Antonia D'Errico-Grigioni, Claudio Franceschi

Research output: Contribution to journalArticle

Abstract

Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive (α4 and β1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28αβ regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical data have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive protea-some and immunoproteasome subunits, as well as PA28αβ. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.

Original languageEnglish
Pages (from-to)301-306
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume397
Issue number2
DOIs
Publication statusPublished - Jun 25 2010

Keywords

  • Chronic active hepatitis
  • Cirrhosis
  • Fetal liver
  • Immunohistochemistry
  • Immunoproteasome
  • Inflammation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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