1: Biochem J 1995 Sep 15;310 ( Pt 3):893-6
Homocysteine enhances the inhibitory effect of extracellular adenosine
on the synthesis of proteins in isolated rat hepatocytes.
Tinton S, Buc-Calderon P
Departement des Sciences Pharmaceutiques, Universite Catholique de Louvain,
Bruxelles, Belgium.
Previous work has shown that extracellular adenosine inhibits the incorporation
of radiolabelled leucine into proteins in isolated rat hepatocytes [Tinton,
Lefebvre, Cousin and Buc Calderon (1993) Biochim. Biophys. Acta 1176, 1-6].
In this study, we investigated whether its metabolism into adenine nucleotides,
inosine or S-adenosylhomocysteine (AdoHcy) is required to induce such an
impairment. Incubation of isolated hepatocytes in the presence of adenosine
at 0.5 or 1 mM reduces the synthesis of proteins by about 45% after 120
min of incubation. Such an inhibition occurred without cell lysis and was
not modified by adding the adenosine kinase inhibitor 5-iodotubercidin
(15 microM) or the adenosine deaminase inhibitor coformycin (0.1 microM).
It is therefore unlikely that the anabolic and catabolic pathways of adenosine
are involved in the inhibition of protein synthesis. Adenosine (1 mM) increased
the level of AdoHcy and S-adenosylmethionine by 20- and 5-fold respectively
after 60 min of incubation and reduced the methylation index. These events
as well as the inhibition of protein synthesis were strongly enhanced in
the presence of L-homocysteine (2 mM). It is therefore concluded that the
metabolism of adenosine into AdoHcy, which is known to be a potent inhibitor
of cellular methylation reactions, may play an important role in the control
of translation.
PMID: 7575424, UI: 96013189