Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network

Abstract Apoptosis and hypertrophy of cardiomyocytes are the primary causes of heart failure and are known to be regulated by complex interactions in the underlying intracellular signaling network. Previous experimental studies were successful in identifying some key signaling components, but most o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jun Hyuk Kang, Ho-Sung Lee, Daebeom Park, Yun-Won Kang, Seon Myeong Kim, Jeong-Ryeol Gong, Kwang-Hyun Cho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7c5a8e254b8848e599231f251bedeb6d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7c5a8e254b8848e599231f251bedeb6d
record_format	dspace
spelling	oai:doaj.org-article:7c5a8e254b8848e599231f251bedeb6d2021-12-02T16:06:45ZContext-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network10.1038/s41598-017-00086-y2045-2322https://doaj.org/article/7c5a8e254b8848e599231f251bedeb6d2017-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00086-yhttps://doaj.org/toc/2045-2322Abstract Apoptosis and hypertrophy of cardiomyocytes are the primary causes of heart failure and are known to be regulated by complex interactions in the underlying intracellular signaling network. Previous experimental studies were successful in identifying some key signaling components, but most of the findings were confined to particular experimental conditions corresponding to specific cellular contexts. A question then arises as to whether there might be essential regulatory interactions that prevail across diverse cellular contexts. To address this question, we have constructed a large-scale cardiac signaling network by integrating previous experimental results and developed a mathematical model using normalized ordinary differential equations. Specific cellular contexts were reflected to different kinetic parameters sampled from random distributions. Through extensive computer simulations with various parameter distributions, we revealed the five most essential context-independent regulatory interactions (between: (1) αAR and Gαq, (2) IP3 and calcium, (3) epac and CaMK, (4) JNK and NFAT, and (5) p38 and NFAT) for hypertrophy and apoptosis that were consistently found over all our perturbation analyses. These essential interactions are expected to be the most promising therapeutic targets across a broad spectrum of individual conditions of heart failure patients.Jun Hyuk KangHo-Sung LeeDaebeom ParkYun-Won KangSeon Myeong KimJeong-Ryeol GongKwang-Hyun ChoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jun Hyuk Kang Ho-Sung Lee Daebeom Park Yun-Won Kang Seon Myeong Kim Jeong-Ryeol Gong Kwang-Hyun Cho Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network
description	Abstract Apoptosis and hypertrophy of cardiomyocytes are the primary causes of heart failure and are known to be regulated by complex interactions in the underlying intracellular signaling network. Previous experimental studies were successful in identifying some key signaling components, but most of the findings were confined to particular experimental conditions corresponding to specific cellular contexts. A question then arises as to whether there might be essential regulatory interactions that prevail across diverse cellular contexts. To address this question, we have constructed a large-scale cardiac signaling network by integrating previous experimental results and developed a mathematical model using normalized ordinary differential equations. Specific cellular contexts were reflected to different kinetic parameters sampled from random distributions. Through extensive computer simulations with various parameter distributions, we revealed the five most essential context-independent regulatory interactions (between: (1) αAR and Gαq, (2) IP3 and calcium, (3) epac and CaMK, (4) JNK and NFAT, and (5) p38 and NFAT) for hypertrophy and apoptosis that were consistently found over all our perturbation analyses. These essential interactions are expected to be the most promising therapeutic targets across a broad spectrum of individual conditions of heart failure patients.
format	article
author	Jun Hyuk Kang Ho-Sung Lee Daebeom Park Yun-Won Kang Seon Myeong Kim Jeong-Ryeol Gong Kwang-Hyun Cho
author_facet	Jun Hyuk Kang Ho-Sung Lee Daebeom Park Yun-Won Kang Seon Myeong Kim Jeong-Ryeol Gong Kwang-Hyun Cho
author_sort	Jun Hyuk Kang
title	Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network
title_short	Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network
title_full	Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network
title_fullStr	Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network
title_full_unstemmed	Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network
title_sort	context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7c5a8e254b8848e599231f251bedeb6d
work_keys_str_mv	AT junhyukkang contextindependentessentialregulatoryinteractionsforapoptosisandhypertrophyinthecardiacsignalingnetwork AT hosunglee contextindependentessentialregulatoryinteractionsforapoptosisandhypertrophyinthecardiacsignalingnetwork AT daebeompark contextindependentessentialregulatoryinteractionsforapoptosisandhypertrophyinthecardiacsignalingnetwork AT yunwonkang contextindependentessentialregulatoryinteractionsforapoptosisandhypertrophyinthecardiacsignalingnetwork AT seonmyeongkim contextindependentessentialregulatoryinteractionsforapoptosisandhypertrophyinthecardiacsignalingnetwork AT jeongryeolgong contextindependentessentialregulatoryinteractionsforapoptosisandhypertrophyinthecardiacsignalingnetwork AT kwanghyuncho contextindependentessentialregulatoryinteractionsforapoptosisandhypertrophyinthecardiacsignalingnetwork
_version_	1718384850974539776

Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network

Ejemplares similares