1: Eur J Biochem 1997 Oct 1;249(1):121-6
Role of protein-phosphorylation events in the anoxia signal-transduction
pathway leading to the inhibition of total protein synthesis in isolated
hepatocytes.
Tinton S, Tran-Nguyen QN, Buc-Calderon P
Departement des Sciences Pharmaceutiques, Universite Catholique de Louvain,
Brussels, Belgium.
Incubation of isolated hepatocytes under N2/CO2 (no O2) produced a rapid
and strong inhibition of overall polypeptide biosynthesis, which was neither
related to cell death nor to the appearance of specific stress proteins.
Treatment of the cells with the tyrosine-kinase inhibitor genistein or
with the serine/threonine-protein-kinase inhibitor H7 did not modify the
impairment of protein synthesis induced by oxygen deprivation, indicating
that such signal-transduction pathways are probably not involved in the
anoxia-mediated effect. Okadaic acid (100 nM) and Na3VO4 (1 mM) reduced
the incorporation of [14C]Leu into proteins of hepatocytes maintained under
aerobic conditions (93.3 kPa O2). The effects of oxygen deprivation and
okadaic acid were additive, whereas sodium vanadate did not enhance the
impairment of protein synthesis induced by anoxia. This observation suggests
that a common mechanism, involving the net phosphorylation of protein tyrosine
residues, that is insensitive to genistein might participate in the negative
control of the translation induced by oxygen deprivation. The effect of
anoxia on the synthesis of proteins was fully and rapidly reversible upon
the restoration of oxygen supply, thus indicating that hepatocytes are
able to sense O2. Although high concentrations of cobalt chloride partially
mimic the effect of oxygen deprivation on protein biosynthesis, the nature
of such an oxygen sensor remains unknown, and appears unlikely to be a
part of a classic haem protein.
PMID: 9363762, UI: 98028392