Dataset Information

The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction.

ABSTRACT: Although a rising concentration of cytosolic Ca2+ has long been recognized as an essential signal for apoptosis, the dynamical mechanisms by which Ca2+ regulates apoptosis are not clear yet. To address this, we constructed a computational model that integrates known biochemical reactions and can reproduce the dynamical behaviors of Ca2+-induced apoptosis as observed in experiments. Model analysis shows that oscillating Ca2+ signals first convert into gradual signals and eventually transform into a switch-like apoptotic response. Via the two processes, the apoptotic signaling pathway filters the frequency of Ca2+ oscillations effectively but instead responds acutely to their amplitude. Collectively, our results suggest that Ca2+ regulates apoptosis mainly via oscillation amplitude, rather than frequency, modulation. This study not only provides a comprehensive understanding of how oscillatory Ca2+ dynamically regulates the complex apoptotic signaling network but also presents a typical example of how Ca2+ controls cellular responses through amplitude modulation.

SUBMITTER: Qi H

PROVIDER: S-EPMC7644924 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction.

Qi Hong H Li Xiang X Jin Zhen Z Simmen Thomas T Shuai Jianwei J

iScience 20201013 11

Although a rising concentration of cytosolic Ca2+ has long been recognized as an essential signal for apoptosis, the dynamical mechanisms by which Ca2+ regulates apoptosis are not clear yet. To address this, we constructed a computational model that integrates known biochemical reactions and can reproduce the dynamical behaviors of Ca2+-induced apoptosis as observed in experiments. Model analysis shows that oscillating Ca2+ signals first convert into g ...[more]

PMID: 33196017

Similar Datasets

Project description:Liver regeneration is regulated by growth factors, cytokines, and other endocrine and metabolic factors. Calcium is important for cell division, but its role in liver regeneration is not known. The purpose of this study was to understand the effects of cytosolic calcium signals in liver growth after partial hepatectomy (PH). The gene encoding the calcium-binding protein parvalbumin (PV) targeted to the cytosol using a nuclear export sequence (NES), and using a discosoma red fluorescent protein (DsR) marker, was transfected into rat livers by injecting it, in recombinant adenovirus (Ad), into the portal vein. We performed two-thirds PH 4 days after Ad-PV-NES-DsR or Ad-DsR injection, and liver regeneration was analyzed. Calcium signals were analyzed with fura-2-acetoxymethyl ester in hepatocytes isolated from Ad-infected rats and in Ad-infected Hela cells. Also, isolated hepatocytes were infected with Ad-DsR or Ad-PV-NES-DsR and assayed for bromodeoxyuridine incorporation. Ad-PV-NES-DsR injection resulted in PV expression in the hepatocyte cytosol. Agonist-induced cytosolic calcium oscillations were attenuated in both PV-NES-expressing Hela cells and hepatocytes, as compared to DsR-expressing cells. Bromodeoxyuridine incorporation (S phase), phosphorylated histone 3 immunostaining (mitosis), and liver mass restoration after PH were all significantly delayed in PV-NES rats. Reduced cyclin expression and retinoblastoma protein phosphorylation confirmed this observation. PV-NES rats exhibited reduced c-fos induction and delayed extracellular signal-regulated kinase 1/2 phosphorylation after PH. Finally, primary PV-NES-expressing hepatocytes exhibited less proliferation and agonist-induced cyclic adenosine monophosphate responsive element binding and extracellular signal-regulated kinase 1/2 phosphorylation, as compared with control cells.Cytosolic calcium signals promote liver regeneration by enhancing progression of hepatocytes through the cell cycle.

Dataset Information

The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction.

Publications

The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets