Effects of chronic ethanol administration on rat liver proteasome activities: Relationship with oxidative stress

Abstract

We previously reported that ethanol elicits an increased protein oxidation in the liver of rats receiving chronic ethanol by continuous intragastric infusion (TsukamotoFrench method). This accumulation of oxidized proteins could result from a decrease in the cytosolic proteolysis, related specifically to alkaline protease and its major components, the proteasomes. Because several studies suggest that intracellular proteolysis depends on the severity of oxidative stress, we investigated the cytosolic proteolytic activity under two chronic ethanol treatment paradigms associated with varying degrees of oxidative stress.

p62 Is a Common Component of Cytoplasmic Inclusions in Protein Aggregation Diseases

“…41 Furthermore, chronic stress may result in impairment of the proteasome degradation machinery. 42 With regard to MB formation it is noteworthy that chronic oxidative stress seems to be involved in all human diseases associated with MB occurrence, such as alcoholic and non-alcoholic steatohepatitis as well as drug-induced liver injury. 42,43 Moreover, chronic oxidative stress might also be the common pathogenetic principle in neurodegenerative diseases featuring cytoplasmic inclusions.…”

“…42 With regard to MB formation it is noteworthy that chronic oxidative stress seems to be involved in all human diseases associated with MB occurrence, such as alcoholic and non-alcoholic steatohepatitis as well as drug-induced liver injury. 42,43 Moreover, chronic oxidative stress might also be the common pathogenetic principle in neurodegenerative diseases featuring cytoplasmic inclusions. 44 -46 It is interesting in this context, particularly with respect to chronic neurodegenerative diseases associated with ubiquitinated neuronal protein inclusions and apoptotic cell death, that p62 is up-regulated in cultured neuronal cells during initiation of apoptosis and proteasomal inhibition.…”

Alcohol and HIV decrease proteasome and immunoproteasome function in macrophages: implications for impaired immune function during disease

“…EtOH treatment did not affect the activity or expression of PR in uninfected MDM, but it attenuated both IFN-c-induced PR activity (predominantly associated with IPR) and enhanced LMP2/LMP7 expression in MDM. Currently, EtOH-induced inhibition of PR activity was demonstrated only in liver tissue derived from EtOH-fed rats and mice [29,43] and in hepatoma cell lines treated with EtOH (HepG2) [44]. In vivo studies suggest more prominent impairment of 26S rather than 20S PR with EtOH treatment.…”

The Effect of CYP2E1-Dependent Oxidant Stress on Activity of Proteasomes in HepG2 Cells

“…The ethanol-inducible CYP2E1 is a catalyst of ROS production and lipid peroxidation in vitro (Ekstrom and Ingelman-Sundberg, 1989). CYP2E1 induction by ethanol is associated with increased oxidative stress in the liver of ethanol-fed rodents (Nanji et al, 1994;Fataccioli et al, 1999). Intragastric administration of ethanol caused a 35 to 40% decline in the ChT-L proteasome activity in rat liver (Fataccioli et al, 1999).…”

“…CYP2E1 induction by ethanol is associated with increased oxidative stress in the liver of ethanol-fed rodents (Nanji et al, 1994;Fataccioli et al, 1999). Intragastric administration of ethanol caused a 35 to 40% decline in the ChT-L proteasome activity in rat liver (Fataccioli et al, 1999). Decreased proteasome activity was associated with increased severity of liver pathology and oxidative stress in alcohol-treated rats (Donohue et al, 2004).…”