Inhibition of albumin synthesis in chronic diseases: molecular mechanisms

J Clin Gastroenterol. 2005 Apr;39(4 Suppl 2):S143-6. doi: 10.1097/01.mcg.0000155514.17715.39.

Abstract

The albumin gene is expressed specifically in the liver after birth, and this expression is regulated predominantly at the transcriptional level. Regulatory proteins occupy specific DNA sequences within the promoter and enhancer of the albumin gene. The interaction between the CCAAT/enhancer binding protein (C/EBP)-beta and the albumin DNA is critical for albumin synthesis. Cachexia-induced hypoalbuminemia is mediated by tumor necrosis factor (TNF)-alpha. In turn, TNF-alpha stimulates oxidative stress, NO synthesis, and phosphorylation of C/EBP-beta within its nuclear localization signal (NLS). Consequently, C/EBP-beta is exported from the nucleus, preventing it to act as a transcriptional factor on the albumin gene. Antioxidants, NOS inhibitors. and dominant negative, nonphosphorylatable C/EBP-beta peptides block phosphorylation of C/EBP-beta within the NLS and its nuclear export as well as rescue the abnormal albumin gene expression, suggesting potential therapeutic interventions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Albumins / biosynthesis*
  • Albumins / genetics
  • Albumins / physiology
  • Animals
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cachexia / metabolism
  • Humans
  • Liver / metabolism*
  • Mice
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Albumins
  • CCAAT-Enhancer-Binding Proteins
  • Tumor Necrosis Factor-alpha