Abstract:

Objective      To study the potential correlation between inhibited proteasome activity and occurrence and development of endoplasmic reticulum stress(ERS) in alcoholic liver disease(ALD). Methods      HepG2 cells were treated  with  ethanol to establish an in vitro model of ALD, and then treated with betulinic acid or with both ethanol and betulinic acid. The mRNA expression of glucose regulation protein 78 (GRP78), a ERS marker, was detected. Also, proteasome activity and intracellular triglyceride(TG) content in different groups were detected. Results      Ethanol inhibited activity of proteasome, with increases of GRP78 mRNA expression and intracellular TG content. Betulinic acid promoted the proteasome activity with reductions of GRP78 mRNA level and TG content. Correlation analysis revealed a negative relativity between proteasome activity and expression of GRP78 mRNA. While the GRP78 mRNA level and intracellular TG content had a positive relativity. Conclusion      Ethanol can inhibit proteasome activity, thus inducing ERS, while betulinic acid can promote proteasome activity, thus reducing ERS. The proteasome activity and ERS have some negative relativity, and the latter aggravates pathogenesis of ALD.

Key words: Liver disease, alcoholic; Endoplasimic reticulum stress; Ubiquitin proteasome