Melatonin as the most effective organizer of the rhythm of protein synthesis in hepatocytes in vitro and in vivo

Abstract

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.

Advances in the Research of Melatonin in Autism Spectrum Disorders: Literature Review and New Perspectives

“…The latter is essential for the daily balance of carbohydrate and lipid metabolism [36]. Finally, melatonin regulates oscillation of CLOCK genes in healthy and cancerous human breast epithelial cells [37], induces a shift in the 24-h oscillatory expression of PER2 and BMAL1 in cultured fetal adrenal gland [38] and influences rhythmic circadian modulation protein synthesis in hepatocytes [39] and erythrocytes [40]. …”

Unmasking ultradian rhythms in gene expression

“…When investigated in mammals, ultradian locomotor rhythmicity is independent of the central circadian clock, and brain substrates such as the retrochiasmatic area of the hypothalamus (16) and the midbrain dopaminergic system (12) have been found to be involved in driving these ultradian patterns. Moreover, ultradian rhythms in in vitro cell cultures have been reported for glucocorticoid release (17, 18), single‐cell firing (19), and protein synthesis (20) suggesting that these rhythms are intrinsically driven at the cellular level, but mechanisms driving them remain unknown.…”

Dose-dependent beneficial effect of melatonin on obesity; interaction of melatonin and leptin

“…Although the mechanisms are not completely understood, the synthesis and actions of melatonin and leptin seem to regulate each other. Moreover, the role of melatonin in protein synthesis regulation is well documented (36,37). We conclude that melatonin drives dosedependent effects in tissues and strongly suggests the use of melatonin in obesity management since it is implicated in the regulation of adipokine secretion.…”