Melatonin Modifies the Rhythm of Protein Synthesis

Brodsky, V. Ya.; Dubovaya, N. D.; Zvezdina, T. K.; Fateeva, V. I.; Мальченко, Л. А.

doi:10.1007/s10517-010-0870-y

Cited by 3 publications

(3 citation statements)

References 10 publications

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“…It was reported that biological oscillations of the intracellular concentrations of autophagosomes/autolysosomes [28][29][30][31][32][33][34][35] and proteins/organelles [36][37][38][39][40] are successfully reproduced in the autophagy system based on the minimal mathematical model. 11 This certainly strengthens the validity of our approach through mathematical modeling and simulations in the autophagy research.…”

Section: Oscillatory Behaviors In the Autophagy Systemmentioning

confidence: 99%

Computer Simulations Unveil the Dynamics of Autophagy and Its Implications for the Cellular Quality Control

2014

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Since the discovery of autophagy half a century ago, a number of physiological and molecular-level studies of autophagy have been carried out, revealing the basic mechanism and role of autophagy in the protein and organelle quality control. However, a reliable assessment method for the autophagy-mediated protein/organelle quality control with the help of an adequate mathematical model has not yet been reported. Based on the previous mathematical modeling of autophagy, we have carried out simulations to prove whether and how basal autophagy achieves substrate specificity and contributes to the cellular protein/organelle quality control. By means of numerical simulations, we probe the selective autophagic mode and observe that autophagic fluxes from abnormal protein/organelle are much greater than those from resident protein/organelle. Such a selective autophagic mode is found to correlate with the fractional abnormal protein/organelle concentration. Finally, it is shown that the fractional abnormal protein/organelle concentration against cellular damaging is efficiently controlled and regulated by suppression or promotion of the autophagosome formation rate. Mathematical modeling and numerical simulations allow one to analyze the autophagic protein/organelle quality control in a specific and quantitative manner and disclose that autophagy serves as a critical cellular quality control mechanism.

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Section: Oscillatory Behaviors In the Autophagy Systemmentioning

confidence: 99%

Computer Simulations Unveil the Dynamics of Autophagy and Its Implications for the Cellular Quality Control

2014

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“…In our first series of experiments (Brodsky, 2008, 2009, 2010a), primary cultures of rat hepatocytes on slides in serum‐free medium were studied. Hepatocytes of adult rat are mature and represent a largely non‐proliferating cell population.…”

Section: Melatonin As a Synchronizer Of Protein Synthesis Oscillatmentioning

confidence: 99%

“…The crucial experiment was performed by adding 2 nM melatonin to the culture medium of dense cultures, which shifts the synthetic rhythm out of a phase (Brodsky et al, 2010a). Thus, the chain of processes resulting in the onset of the rhythm from chaotic oscillations may be presented as follows: signal factor (melatonin) → elevation of Ca +2 content in the cell cytoplasm → stimulation of protein kinase (mainly protein kinase C) activity → protein phosphorylation → shifts in individual cell rhythms and coordination accordingly of protein synthesis oscillations throughout cell population → common rhythm throughout the cell population.…”

Section: Melatonin As a Synchronizer Of Protein Synthesis Oscillatmentioning

confidence: 99%

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

Brodsky

Zvezdina

2010

Cell Biology International

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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.

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Quantitative indices of autophagy activity from minimal models

Han

Kim

Choi

2014

Theor Biol Med Model

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BackgroundA number of cellular- and molecular-level studies of autophagy assessment have been carried out with the help of various biochemical and morphological indices. Still there exists ambiguity for the assessment of the autophagy status and of the causal relationship between autophagy and related cellular changes. To circumvent such difficulties, we probe new quantitative indices of autophagy which are important for defining autophagy activation and further assessing its roles associated with different physiopathological states.MethodsOur approach is based on the minimal autophagy model that allows us to understand underlying dynamics of autophagy from biological experiments. Specifically, based on the model, we reconstruct the experimental context-specific autophagy profiles from the target autophagy system, and two quantitative indices are defined from the model-driven profiles. The indices are then applied to the simulation-based analysis, for the specific and quantitative interpretation of the system.ResultsTwo quantitative indices measuring autophagy activities in the induction of sequestration fluxes and in the selective degradation are proposed, based on the model-driven autophagy profiles such as the time evolution of autophagy fluxes, levels of autophagosomes/autolysosomes, and corresponding cellular changes. Further, with the help of the indices, those biological experiments of the target autophagy system have been successfully analyzed, implying that the indices are useful not only for defining autophagy activation but also for assessing its role in a specific and quantitative manner.ConclusionsSuch quantitative autophagy indices in conjunction with the computer-aided analysis should provide new opportunities to characterize the causal relationship between autophagy activity and the corresponding cellular change, based on the system-level understanding of the autophagic process at good time resolution, complementing the current in vivo and in vitro assays.

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Melatonin Modifies the Rhythm of Protein Synthesis

Cited by 3 publications

References 10 publications

Computer Simulations Unveil the Dynamics of Autophagy and Its Implications for the Cellular Quality Control

Computer Simulations Unveil the Dynamics of Autophagy and Its Implications for the Cellular Quality Control

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

Quantitative indices of autophagy activity from minimal models

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