Mallory bodies (MB) are a significant component of liver injury on many different diseases of the liver but the pathogenesis of MBs is unknown, largely because MBs appear late in chronic liver disease. Recently we developed a acute model of MB formation after mice had been fed DDC for 5 months then withdrawn from the drug for 1 month when the MBs had disappeared. The MBs reappeared in 3-7 days of refeeding or after heat shock or thioacetamide treatment. Now we report that MBs reappear within 7 days of feeding ethanol (14-15 g/kg/d) or after IP injection of D-galactosamine (2 g/kg) or okadaic acid (210 μg/kg). Controls for ethanol were pair fed glucose by continuous tube feeding. Liver biopsies taken before feeding ethanol served as their own controls. Controls for okadaic received the vehicle IP. Gel shift assays done on nuclear extracts from the okadaic acid treated mice showed that MB formation was associated with NFκB activation, but gel supershift assay showed a positive shift with p65 aminoterminal antibody but not p65 carboxyterminal antibody indicating that activation of NFκB was followed by proteolysis of p65 to p35. The results suggested that NFκB activation may be a common denominator which underlies MB formation.
|Original language||English (US)|
|State||Published - 1997|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology