Modifications in P62 occur due to proteasome inhibition in alcoholic liver disease

P62 is capable of binding the polyubiquitin chain that targets proteins for degradation by the proteasome through its ubiquitin associated domain (UBA). Immunostaining of hepatocytes from human liver with alcoholic hepatitis showed colocalization of ubiquitin and P62 in Mallory bodies. Rats fed etha...

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Bibliographic Details
Published in:Life sciences (1973) 2005-09, Vol.77 (20), p.2594-2602
Main Authors: Bardag-Gorce, Fawzia, Francis, Tricia, Nan, Li, Li, Jun, He Lue, Yan, French, Barbara A., French, Samuel W.
Format: Article
Language:English
Subjects:
Alcoholic liver disease
Animals
Blotting, Western
Heat-Shock Proteins - metabolism
Hepatitis, Animal - enzymology
Hepatitis, Animal - metabolism
Immunohistochemistry
Liver - enzymology
Liver - metabolism
Liver Diseases, Alcoholic - enzymology
Liver Diseases, Alcoholic - metabolism
Male
P62
Proteasome Endopeptidase Complex
Proteasome inhibition
Proteasome Inhibitors
Rats
Rats, Wistar
Sequestosome-1 Protein
Ubiquitin - metabolism
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Summary:P62 is capable of binding the polyubiquitin chain that targets proteins for degradation by the proteasome through its ubiquitin associated domain (UBA). Immunostaining of hepatocytes from human liver with alcoholic hepatitis showed colocalization of ubiquitin and P62 in Mallory bodies. Rats fed ethanol chronically and their controls showed that P62 is colocalized with the proteasome in hepatocytes as shown by confocal microscopy. P62 cosedimented with 26S proteasomes isolated from livers of control and alcohol fed rats. P62 was increased in the 26S proteasome fraction when the proteasome chymotrypsin-like (ChT-L) activity decreased in rats fed ethanol. PS-341, a potent proteasome inhibitor was used to compare the inhibition of the proteasome with the inhibition which occurs with ethanol feeding. P62 protein levels were also increased in the purified proteasome fraction of rats given PS-341. This data indicates that modifications in P62 occur due to proteasome inhibition in experimental alcoholic liver disease.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2005.04.020