Hypoxia increases the association of 4E-binding protein 1 with the initiation factor 4E in isolated rat hepatocytes

FEBS Lett. 1999 Mar 5;446(1):55-9. doi: 10.1016/s0014-5793(99)00185-4.

Abstract

Incubation of hepatocytes under hypoxia increases binding of translation initiation factor eIF-4E to its inhibitory regulator 4E-BP1, and this correlates with dephosphorylation of 4E-BP1. Rapamycin induced the same effect in aerobic cells but no additive effect was observed when hypoxic cells were treated with rapamycin. This enhanced association of 4E-BP1 with eIF-4E might be mediated by mTOR. Nevertheless, only hypoxia produces a rapid inhibition of protein synthesis. Although hypoxia might be signalling via the rapamycin-sensitive pathway by changing eIF-4E availability, such a pathway is unlikely to be responsible for the depression in overall protein synthesis under hypoxia.

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology
  • Carrier Proteins*
  • Cell Hypoxia
  • Cells, Cultured
  • Eukaryotic Initiation Factor-4E
  • Intracellular Signaling Peptides and Proteins
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Peptide Initiation Factors / metabolism*
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Sirolimus / pharmacology

Substances

  • Antifungal Agents
  • Carrier Proteins
  • Eif4ebp1 protein, rat
  • Eukaryotic Initiation Factor-4E
  • Intracellular Signaling Peptides and Proteins
  • Peptide Initiation Factors
  • Phosphoproteins
  • Sirolimus