Cargando…

PEDF Inhibits the Activation of NLRP3 Inflammasome in Hypoxia Cardiomyocytes through PEDF Receptor/Phospholipase A2

The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome has been linked to sterile inflammation, which is involved in ischemic injury in myocardial cells. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein with many biological activ...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Zhongxin, Wang, Zhu, Guan, Qiuhua, Qiu, Fan, Li, Yufeng, Liu, Zhiwei, Zhang, Hao, Dong, Hongyan, Zhang, Zhongming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187864/
https://www.ncbi.nlm.nih.gov/pubmed/27973457
http://dx.doi.org/10.3390/ijms17122064
_version_ 1782486915168075776
author Zhou, Zhongxin
Wang, Zhu
Guan, Qiuhua
Qiu, Fan
Li, Yufeng
Liu, Zhiwei
Zhang, Hao
Dong, Hongyan
Zhang, Zhongming
author_facet Zhou, Zhongxin
Wang, Zhu
Guan, Qiuhua
Qiu, Fan
Li, Yufeng
Liu, Zhiwei
Zhang, Hao
Dong, Hongyan
Zhang, Zhongming
author_sort Zhou, Zhongxin
collection PubMed
description The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome has been linked to sterile inflammation, which is involved in ischemic injury in myocardial cells. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein with many biological activities, such as anti-inflammatory, antioxidant and anti-angiogenic properties. However, it is not known whether and how PEDF acts to regulate the activation of the NLRP3 inflammasome in cardiomyocytes. In the present study, we used the neonatal cardiomyocytes models of ischemia-like conditions to evaluate the mitochondrial fission and the activation of the NLRP3 inflammasome. We also determined the mechanism by which PEDF inhibits hypoxia-induced activation of the NLRP3 inflammasome. We found that PEDF decreased the activation of the NLRP3 inflammasome in neonatal cardiomyocytes through pigment epithelial-derived factor receptor/calcium-independent phospholipase A2 (PEDFR/iPLA2). Meanwhile, PEDF reduced Drp1-induced mitochondrial fission and mitochondrial fission-induced mitochondrial DNA (mtDNA), as well as mitochondrial reactive oxygen species (mtROS) release into cytosol through PEDFR/iPLA2. We also found that PEDF inhibited mitochondrial fission-induced NLRP3 inflammasome activation. Furthermore, previous research has found that endogenous cytosolic mtDNA and mtROS can serve as activators of NLRP3 inflammasome activity. Therefore, we hypothesized that PEDF can protect against hypoxia-induced activation of the NLRP3 inflammasome by inhibiting mitochondrial fission though PEDFR/iPLA2.
format Online
Article
Text
id pubmed-5187864
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-51878642016-12-30 PEDF Inhibits the Activation of NLRP3 Inflammasome in Hypoxia Cardiomyocytes through PEDF Receptor/Phospholipase A2 Zhou, Zhongxin Wang, Zhu Guan, Qiuhua Qiu, Fan Li, Yufeng Liu, Zhiwei Zhang, Hao Dong, Hongyan Zhang, Zhongming Int J Mol Sci Article The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome has been linked to sterile inflammation, which is involved in ischemic injury in myocardial cells. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein with many biological activities, such as anti-inflammatory, antioxidant and anti-angiogenic properties. However, it is not known whether and how PEDF acts to regulate the activation of the NLRP3 inflammasome in cardiomyocytes. In the present study, we used the neonatal cardiomyocytes models of ischemia-like conditions to evaluate the mitochondrial fission and the activation of the NLRP3 inflammasome. We also determined the mechanism by which PEDF inhibits hypoxia-induced activation of the NLRP3 inflammasome. We found that PEDF decreased the activation of the NLRP3 inflammasome in neonatal cardiomyocytes through pigment epithelial-derived factor receptor/calcium-independent phospholipase A2 (PEDFR/iPLA2). Meanwhile, PEDF reduced Drp1-induced mitochondrial fission and mitochondrial fission-induced mitochondrial DNA (mtDNA), as well as mitochondrial reactive oxygen species (mtROS) release into cytosol through PEDFR/iPLA2. We also found that PEDF inhibited mitochondrial fission-induced NLRP3 inflammasome activation. Furthermore, previous research has found that endogenous cytosolic mtDNA and mtROS can serve as activators of NLRP3 inflammasome activity. Therefore, we hypothesized that PEDF can protect against hypoxia-induced activation of the NLRP3 inflammasome by inhibiting mitochondrial fission though PEDFR/iPLA2. MDPI 2016-12-12 /pmc/articles/PMC5187864/ /pubmed/27973457 http://dx.doi.org/10.3390/ijms17122064 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhou, Zhongxin
Wang, Zhu
Guan, Qiuhua
Qiu, Fan
Li, Yufeng
Liu, Zhiwei
Zhang, Hao
Dong, Hongyan
Zhang, Zhongming
PEDF Inhibits the Activation of NLRP3 Inflammasome in Hypoxia Cardiomyocytes through PEDF Receptor/Phospholipase A2
title PEDF Inhibits the Activation of NLRP3 Inflammasome in Hypoxia Cardiomyocytes through PEDF Receptor/Phospholipase A2
title_full PEDF Inhibits the Activation of NLRP3 Inflammasome in Hypoxia Cardiomyocytes through PEDF Receptor/Phospholipase A2
title_fullStr PEDF Inhibits the Activation of NLRP3 Inflammasome in Hypoxia Cardiomyocytes through PEDF Receptor/Phospholipase A2
title_full_unstemmed PEDF Inhibits the Activation of NLRP3 Inflammasome in Hypoxia Cardiomyocytes through PEDF Receptor/Phospholipase A2
title_short PEDF Inhibits the Activation of NLRP3 Inflammasome in Hypoxia Cardiomyocytes through PEDF Receptor/Phospholipase A2
title_sort pedf inhibits the activation of nlrp3 inflammasome in hypoxia cardiomyocytes through pedf receptor/phospholipase a2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187864/
https://www.ncbi.nlm.nih.gov/pubmed/27973457
http://dx.doi.org/10.3390/ijms17122064
work_keys_str_mv AT zhouzhongxin pedfinhibitstheactivationofnlrp3inflammasomeinhypoxiacardiomyocytesthroughpedfreceptorphospholipasea2
AT wangzhu pedfinhibitstheactivationofnlrp3inflammasomeinhypoxiacardiomyocytesthroughpedfreceptorphospholipasea2
AT guanqiuhua pedfinhibitstheactivationofnlrp3inflammasomeinhypoxiacardiomyocytesthroughpedfreceptorphospholipasea2
AT qiufan pedfinhibitstheactivationofnlrp3inflammasomeinhypoxiacardiomyocytesthroughpedfreceptorphospholipasea2
AT liyufeng pedfinhibitstheactivationofnlrp3inflammasomeinhypoxiacardiomyocytesthroughpedfreceptorphospholipasea2
AT liuzhiwei pedfinhibitstheactivationofnlrp3inflammasomeinhypoxiacardiomyocytesthroughpedfreceptorphospholipasea2
AT zhanghao pedfinhibitstheactivationofnlrp3inflammasomeinhypoxiacardiomyocytesthroughpedfreceptorphospholipasea2
AT donghongyan pedfinhibitstheactivationofnlrp3inflammasomeinhypoxiacardiomyocytesthroughpedfreceptorphospholipasea2
AT zhangzhongming pedfinhibitstheactivationofnlrp3inflammasomeinhypoxiacardiomyocytesthroughpedfreceptorphospholipasea2