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Cell Biology International (2010) 34, 1199–1204 (Printed in Great Britain)
Review article
Melatonin as the most effective organizer of the rhythm of protein synthesis in hepatocytes in vitro and in vivo
Vsevolod Y Brodsky1 and Natalia D Zvezdina
Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov street, 119334 Moscow, Russia


Recent data has extended a large array of melatonin functions by the discovery of melatonin's involvement in the organization and regulation of the rhythm of intracellular protein synthesis. An ultradian rhythm in total protein synthesis has been detected in primary hepatocyte cultures 5 min after addition of 1–5 nM melatonin to the medium. The melatonin effect was mediated via its receptors (as shown in experiments with luzindole), leading to the cell synchronization as well as the mean rate of protein synthesis rate being increased. The chain of processes synchronizing the oscillation of the rate protein synthesis throughout the hepatocyte population includes Ca2+ fluxes {experiments with BAPTA-AM [1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (acetomethyl ester)]}. Inhibition of protein kinase activity (experiments with H7) inhibited the synchronizing function of melatonin. Activation of protein kinase activity results in a shift of the protein synthesis oscillation; the effect was the same as melatonin added to the culture medium. In another series of experiments, after melatonin was intraperitoneally injected to rat (0.015–0.020 μg/kg), hepatocytes were isolated and cultures established. A synchronizing effect of melatonin in vivo was detected as early as in the estimates from the direct action of melatonin on cell cultures. In the cultures obtained from old rats provided with melatonin, the amplitude of protein synthesis rhythm was enhanced, i.e. cell–cell interactions were increased, as well as rate of the protein synthesis being enhanced.


Key words: aging, cell–cell interaction, hepatocyte, melatonin, protein synthesis rhythm, signal factor, ultradian rhythm

Abbreviations: BAPTA-AM, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (acetomethyl ester), PPPP, d-l-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol-HCL

1To whom correspondence should be addressed (email brodsky.idb@bk.ru).

Part of a series marking the 70th birthday of the Cell Biology International Editor-in-Chief Denys Wheatley


Received 3 July 2010; accepted 26 July 2010

Published online 25 October 2010, doi:10.1042/CBI20100036


© The Author(s) Journal compilation © 2010 Portland Press Limited


ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)