title: Modifications in P62 occur due to proteasome inhibition in alcoholic liver disease.
abstract: 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.
authors.affiliation: Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
authors.forename: Fawzia
authors.initials: F
authors.lastname: Bardag-Gorce
authors.forename: Tricia
authors.initials: T
authors.lastname: Francis
authors.forename: Li
authors.initials: L
authors.lastname: Nan
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: He Lue
authors.forename: Barbara A
authors.initials: BA
authors.lastname: French
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006520:Hepatitis, Animal / Q000201:enzymology / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors; D051381:Rats; D017208:Rats, Wistar; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D061988:Proteasome Inhibitors; D000071456:Sequestosome-1 Protein; C491079:Sqstm1 protein, rat; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease