1: Biochem Pharmacol 1995 Aug 8;50(4):481-8
Inhibition of protein synthesis induced by adenine nucleotides requires
their metabolism into adenosine.
Tinton S, Buc-Calderon P
Department des Sciences Pharmaceutiques, Universite Catholique de Louvain,
Bruxelles, Belgium.
Adenine nucleotides and adenosine inhibit the incorporation of radiolabelled
leucine into proteins of isolated hepatocytes. Impairment occurred with
nucleotides which can be converted into 9-beta-D-ribofuranosyladenine (adenosine)
but was not observed after treatment with adenine or AMPCPP (the alpha,
beta-methylene analogue of ATP). Metabolism into adenosine was further
suggested by the increase in cellular ATP levels following treatment of
hepatocytes with ATP, adenosine or AMPPCP (the beta, gamma-methylene ATP
analogue) while AMPCPP was without any significant effect. The inhibition
of protein synthesis caused by adenosine was not due to a lytic effect
nor to a general disturbance in hepatic functions and was reversed when
the cells were washed and transferred to a nucleoside-free medium. This
impairment, however, was not coupled to the activation of adenylate cyclase,
as preincubation of hepatocytes with P1 purinoceptor antagonists failed
to prevent protein synthesis inhibition. In contrast, L-homocysteine enhanced
the inhibitory effect of adenosine on the incorporation of radiolabelled
leucine into proteins. Our results thus suggest that the inhibition of
protein synthesis caused by adenine nucleotides requires their conversion
into adenosine. They also indicate that the inhibitory effect of adenosine
does not involve a receptor-mediated effect but may be related to an increase
in S-adenosylhomocysteine content and a subsequent low level of macromolecule
methylation.
PMID: 7646553, UI: 95374565