Cargando…
Overexpression of Hypo-Phosphorylated IκBβ at Ser313 Protects the Heart against Sepsis
IκBβis an inhibitor of nuclear factor kappa B(NF-κB) and participates in the cardiac response to sepsis. However, the role of the hypo-phosphorylated form of IκBβ at Ser313, which can be detected during sepsis, is unknown. Here, we examined the effects of IκBβ with a mutation at Ser313→Ala313 on car...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979969/ https://www.ncbi.nlm.nih.gov/pubmed/27508931 http://dx.doi.org/10.1371/journal.pone.0160860 |
_version_ | 1782447408205004800 |
---|---|
author | Wang, Guang-Qing Tang, Tao Wang, Zhong-Shan Liu, Ying-Ying Wang, Li Luo, Peng-Fei Xia, Zhao-Fan |
author_facet | Wang, Guang-Qing Tang, Tao Wang, Zhong-Shan Liu, Ying-Ying Wang, Li Luo, Peng-Fei Xia, Zhao-Fan |
author_sort | Wang, Guang-Qing |
collection | PubMed |
description | IκBβis an inhibitor of nuclear factor kappa B(NF-κB) and participates in the cardiac response to sepsis. However, the role of the hypo-phosphorylated form of IκBβ at Ser313, which can be detected during sepsis, is unknown. Here, we examined the effects of IκBβ with a mutation at Ser313→Ala313 on cardiac damage induced by sepsis. Transgenic (Tg) mice were generated to overexpress IκBβ, in which Ser-313 is replaced with alanine ubiquitously, in order to mimic the hypo-phosphorylated form of IκBβ. Survival analysis showed that Tg mice exhibited decreased inflammatory cytokine levels and decreased rates of mortality in comparison to wild type (WT) mice, after sepsis in a cecal-ligation and puncture model (CLP). Compared to WT septic mice, sepsis in Tg mice resulted in improved cardiac functions, lower levels of troponin I and decreased rates of cardiomyocyte apoptosis, compared to WT mice. The increased formation of autophagicvacuoles detected with electron microscopy demonstrated the enhancement of cardiac autophagy. This phenomenon was further confirmed by the differential expression of genes related to autophagy, such as LC3, Atg5, Beclin-1, and p62. The increased expression of Cathepsin L(Ctsl), a specific marker for mitochondrial stress response, may be associated with the beneficial effects of the hypo-phosphorylated form of IκBβ. Our observations suggest that the hypo-phosphorylated form of IκBβ at Ser313 is beneficial to the heart in sepsis through inhibition of apoptosisand enhancement of autophagy in mutated IκBβ transgenic mice. |
format | Online Article Text |
id | pubmed-4979969 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-49799692016-08-25 Overexpression of Hypo-Phosphorylated IκBβ at Ser313 Protects the Heart against Sepsis Wang, Guang-Qing Tang, Tao Wang, Zhong-Shan Liu, Ying-Ying Wang, Li Luo, Peng-Fei Xia, Zhao-Fan PLoS One Research Article IκBβis an inhibitor of nuclear factor kappa B(NF-κB) and participates in the cardiac response to sepsis. However, the role of the hypo-phosphorylated form of IκBβ at Ser313, which can be detected during sepsis, is unknown. Here, we examined the effects of IκBβ with a mutation at Ser313→Ala313 on cardiac damage induced by sepsis. Transgenic (Tg) mice were generated to overexpress IκBβ, in which Ser-313 is replaced with alanine ubiquitously, in order to mimic the hypo-phosphorylated form of IκBβ. Survival analysis showed that Tg mice exhibited decreased inflammatory cytokine levels and decreased rates of mortality in comparison to wild type (WT) mice, after sepsis in a cecal-ligation and puncture model (CLP). Compared to WT septic mice, sepsis in Tg mice resulted in improved cardiac functions, lower levels of troponin I and decreased rates of cardiomyocyte apoptosis, compared to WT mice. The increased formation of autophagicvacuoles detected with electron microscopy demonstrated the enhancement of cardiac autophagy. This phenomenon was further confirmed by the differential expression of genes related to autophagy, such as LC3, Atg5, Beclin-1, and p62. The increased expression of Cathepsin L(Ctsl), a specific marker for mitochondrial stress response, may be associated with the beneficial effects of the hypo-phosphorylated form of IκBβ. Our observations suggest that the hypo-phosphorylated form of IκBβ at Ser313 is beneficial to the heart in sepsis through inhibition of apoptosisand enhancement of autophagy in mutated IκBβ transgenic mice. Public Library of Science 2016-08-10 /pmc/articles/PMC4979969/ /pubmed/27508931 http://dx.doi.org/10.1371/journal.pone.0160860 Text en © 2016 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Wang, Guang-Qing Tang, Tao Wang, Zhong-Shan Liu, Ying-Ying Wang, Li Luo, Peng-Fei Xia, Zhao-Fan Overexpression of Hypo-Phosphorylated IκBβ at Ser313 Protects the Heart against Sepsis |
title | Overexpression of Hypo-Phosphorylated IκBβ at Ser313 Protects the Heart against Sepsis |
title_full | Overexpression of Hypo-Phosphorylated IκBβ at Ser313 Protects the Heart against Sepsis |
title_fullStr | Overexpression of Hypo-Phosphorylated IκBβ at Ser313 Protects the Heart against Sepsis |
title_full_unstemmed | Overexpression of Hypo-Phosphorylated IκBβ at Ser313 Protects the Heart against Sepsis |
title_short | Overexpression of Hypo-Phosphorylated IκBβ at Ser313 Protects the Heart against Sepsis |
title_sort | overexpression of hypo-phosphorylated iκbβ at ser313 protects the heart against sepsis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979969/ https://www.ncbi.nlm.nih.gov/pubmed/27508931 http://dx.doi.org/10.1371/journal.pone.0160860 |
work_keys_str_mv | AT wangguangqing overexpressionofhypophosphorylatedikbbatser313protectstheheartagainstsepsis AT tangtao overexpressionofhypophosphorylatedikbbatser313protectstheheartagainstsepsis AT wangzhongshan overexpressionofhypophosphorylatedikbbatser313protectstheheartagainstsepsis AT liuyingying overexpressionofhypophosphorylatedikbbatser313protectstheheartagainstsepsis AT wangli overexpressionofhypophosphorylatedikbbatser313protectstheheartagainstsepsis AT luopengfei overexpressionofhypophosphorylatedikbbatser313protectstheheartagainstsepsis AT xiazhaofan overexpressionofhypophosphorylatedikbbatser313protectstheheartagainstsepsis |