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

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 (alpha4 and beta1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28alphabeta 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 proteasome and immunoproteasome subunits, as well as PA28alphabeta. 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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Vasuri F,Capizzi E,Bellavista E,Mishto M,Santoro A,Fiorentino M,Capri M,Cescon M,Grazi GL,Grigioni WF,D'Errico-Grigioni A,Franceschi C

doi

10.1016/j.bbrc.2010.05.104

subject

Has Abstract

pub_date

2010-06-25 00:00:00

pages

301-6

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(10)01019-3

journal_volume

397

pub_type

杂志文章

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