Cargando…
The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction
Although a rising concentration of cytosolic Ca(2+) has long been recognized as an essential signal for apoptosis, the dynamical mechanisms by which Ca(2+) regulates apoptosis are not clear yet. To address this, we constructed a computational model that integrates known biochemical reactions and can...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644924/ https://www.ncbi.nlm.nih.gov/pubmed/33196017 http://dx.doi.org/10.1016/j.isci.2020.101671 |
_version_ | 1783606555648720896 |
---|---|
author | Qi, Hong Li, Xiang Jin, Zhen Simmen, Thomas Shuai, Jianwei |
author_facet | Qi, Hong Li, Xiang Jin, Zhen Simmen, Thomas Shuai, Jianwei |
author_sort | Qi, Hong |
collection | PubMed |
description | Although a rising concentration of cytosolic Ca(2+) has long been recognized as an essential signal for apoptosis, the dynamical mechanisms by which Ca(2+) 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 Ca(2+)-induced apoptosis as observed in experiments. Model analysis shows that oscillating Ca(2+) 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 Ca(2+) oscillations effectively but instead responds acutely to their amplitude. Collectively, our results suggest that Ca(2+) regulates apoptosis mainly via oscillation amplitude, rather than frequency, modulation. This study not only provides a comprehensive understanding of how oscillatory Ca(2+) dynamically regulates the complex apoptotic signaling network but also presents a typical example of how Ca(2+) controls cellular responses through amplitude modulation. |
format | Online Article Text |
id | pubmed-7644924 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-76449242020-11-13 The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction Qi, Hong Li, Xiang Jin, Zhen Simmen, Thomas Shuai, Jianwei iScience Article Although a rising concentration of cytosolic Ca(2+) has long been recognized as an essential signal for apoptosis, the dynamical mechanisms by which Ca(2+) 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 Ca(2+)-induced apoptosis as observed in experiments. Model analysis shows that oscillating Ca(2+) 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 Ca(2+) oscillations effectively but instead responds acutely to their amplitude. Collectively, our results suggest that Ca(2+) regulates apoptosis mainly via oscillation amplitude, rather than frequency, modulation. This study not only provides a comprehensive understanding of how oscillatory Ca(2+) dynamically regulates the complex apoptotic signaling network but also presents a typical example of how Ca(2+) controls cellular responses through amplitude modulation. Elsevier 2020-10-13 /pmc/articles/PMC7644924/ /pubmed/33196017 http://dx.doi.org/10.1016/j.isci.2020.101671 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Qi, Hong Li, Xiang Jin, Zhen Simmen, Thomas Shuai, Jianwei The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction |
title | The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction |
title_full | The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction |
title_fullStr | The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction |
title_full_unstemmed | The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction |
title_short | The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction |
title_sort | oscillation amplitude, not the frequency of cytosolic calcium, regulates apoptosis induction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644924/ https://www.ncbi.nlm.nih.gov/pubmed/33196017 http://dx.doi.org/10.1016/j.isci.2020.101671 |
work_keys_str_mv | AT qihong theoscillationamplitudenotthefrequencyofcytosoliccalciumregulatesapoptosisinduction AT lixiang theoscillationamplitudenotthefrequencyofcytosoliccalciumregulatesapoptosisinduction AT jinzhen theoscillationamplitudenotthefrequencyofcytosoliccalciumregulatesapoptosisinduction AT simmenthomas theoscillationamplitudenotthefrequencyofcytosoliccalciumregulatesapoptosisinduction AT shuaijianwei theoscillationamplitudenotthefrequencyofcytosoliccalciumregulatesapoptosisinduction AT qihong oscillationamplitudenotthefrequencyofcytosoliccalciumregulatesapoptosisinduction AT lixiang oscillationamplitudenotthefrequencyofcytosoliccalciumregulatesapoptosisinduction AT jinzhen oscillationamplitudenotthefrequencyofcytosoliccalciumregulatesapoptosisinduction AT simmenthomas oscillationamplitudenotthefrequencyofcytosoliccalciumregulatesapoptosisinduction AT shuaijianwei oscillationamplitudenotthefrequencyofcytosoliccalciumregulatesapoptosisinduction |