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

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.