Computational insights on the competing effects of nitric oxide in regulating apoptosis.

Despite the establishment of the important role of nitric oxide (NO) on apoptosis, a molecular-level understanding of the origin of its dichotomous pro- and anti-apoptotic effects has been elusive. We propose a new mathematical model for simulating the effects of nitric oxide (NO) on apoptosis. The...

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Autores principales:	Elife Z Bagci, Yoram Vodovotz, Timothy R Billiar, Bard Ermentrout, Ivet Bahar
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d71f4eb5e41c42e1a5d162a63dfef666
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spelling	oai:doaj.org-article:d71f4eb5e41c42e1a5d162a63dfef6662021-11-25T06:12:17ZComputational insights on the competing effects of nitric oxide in regulating apoptosis.1932-620310.1371/journal.pone.0002249https://doaj.org/article/d71f4eb5e41c42e1a5d162a63dfef6662008-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18509469/?tool=EBIhttps://doaj.org/toc/1932-6203Despite the establishment of the important role of nitric oxide (NO) on apoptosis, a molecular-level understanding of the origin of its dichotomous pro- and anti-apoptotic effects has been elusive. We propose a new mathematical model for simulating the effects of nitric oxide (NO) on apoptosis. The new model integrates mitochondria-dependent apoptotic pathways with NO-related reactions, to gain insights into the regulatory effect of the reactive NO species N(2)O(3), non-heme iron nitrosyl species (FeL(n)NO), and peroxynitrite (ONOO(-)). The biochemical pathways of apoptosis coupled with NO-related reactions are described by ordinary differential equations using mass-action kinetics. In the absence of NO, the model predicts either cell survival or apoptosis (a bistable behavior) with shifts in the onset time of apoptotic response depending on the strength of extracellular stimuli. Computations demonstrate that the relative concentrations of anti- and pro-apoptotic reactive NO species, and their interplay with glutathione, determine the net anti- or pro-apoptotic effects at long time points. Interestingly, transient effects on apoptosis are also observed in these simulations, the duration of which may reach up to hours, despite the eventual convergence to an anti-apoptotic state. Our computations point to the importance of precise timing of NO production and external stimulation in determining the eventual pro- or anti-apoptotic role of NO.Elife Z BagciYoram VodovotzTimothy R BilliarBard ErmentroutIvet BaharPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 5, p e2249 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elife Z Bagci Yoram Vodovotz Timothy R Billiar Bard Ermentrout Ivet Bahar Computational insights on the competing effects of nitric oxide in regulating apoptosis.
description	Despite the establishment of the important role of nitric oxide (NO) on apoptosis, a molecular-level understanding of the origin of its dichotomous pro- and anti-apoptotic effects has been elusive. We propose a new mathematical model for simulating the effects of nitric oxide (NO) on apoptosis. The new model integrates mitochondria-dependent apoptotic pathways with NO-related reactions, to gain insights into the regulatory effect of the reactive NO species N(2)O(3), non-heme iron nitrosyl species (FeL(n)NO), and peroxynitrite (ONOO(-)). The biochemical pathways of apoptosis coupled with NO-related reactions are described by ordinary differential equations using mass-action kinetics. In the absence of NO, the model predicts either cell survival or apoptosis (a bistable behavior) with shifts in the onset time of apoptotic response depending on the strength of extracellular stimuli. Computations demonstrate that the relative concentrations of anti- and pro-apoptotic reactive NO species, and their interplay with glutathione, determine the net anti- or pro-apoptotic effects at long time points. Interestingly, transient effects on apoptosis are also observed in these simulations, the duration of which may reach up to hours, despite the eventual convergence to an anti-apoptotic state. Our computations point to the importance of precise timing of NO production and external stimulation in determining the eventual pro- or anti-apoptotic role of NO.
format	article
author	Elife Z Bagci Yoram Vodovotz Timothy R Billiar Bard Ermentrout Ivet Bahar
author_facet	Elife Z Bagci Yoram Vodovotz Timothy R Billiar Bard Ermentrout Ivet Bahar
author_sort	Elife Z Bagci
title	Computational insights on the competing effects of nitric oxide in regulating apoptosis.
title_short	Computational insights on the competing effects of nitric oxide in regulating apoptosis.
title_full	Computational insights on the competing effects of nitric oxide in regulating apoptosis.
title_fullStr	Computational insights on the competing effects of nitric oxide in regulating apoptosis.
title_full_unstemmed	Computational insights on the competing effects of nitric oxide in regulating apoptosis.
title_sort	computational insights on the competing effects of nitric oxide in regulating apoptosis.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/d71f4eb5e41c42e1a5d162a63dfef666
work_keys_str_mv	AT elifezbagci computationalinsightsonthecompetingeffectsofnitricoxideinregulatingapoptosis AT yoramvodovotz computationalinsightsonthecompetingeffectsofnitricoxideinregulatingapoptosis AT timothyrbilliar computationalinsightsonthecompetingeffectsofnitricoxideinregulatingapoptosis AT bardermentrout computationalinsightsonthecompetingeffectsofnitricoxideinregulatingapoptosis AT ivetbahar computationalinsightsonthecompetingeffectsofnitricoxideinregulatingapoptosis
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Computational insights on the competing effects of nitric oxide in regulating apoptosis.

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