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Apolipoprotein-J blocks increased cell injury elicited by ox-LDL via inhibiting ROS-CaMKII pathway
BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) is crucial in cardiac injury. Apolipoprotein-J (ApoJ) contributes to antiapoptotic effects in the heart. We aimed to evaluate the protective effects of ApoJ against ox-LDL cytotoxicity in Neonatal rat ventricular cells (NRVCs). METHODS AND RESULT...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530009/ https://www.ncbi.nlm.nih.gov/pubmed/31113434 http://dx.doi.org/10.1186/s12944-019-1066-8 |
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author | Ma, Yanzhuo Gong, Zhi Nan, Kai Qi, Shuying Chen, Yu Ding, Chao Wang, Dongmei Ru, Leisheng |
author_facet | Ma, Yanzhuo Gong, Zhi Nan, Kai Qi, Shuying Chen, Yu Ding, Chao Wang, Dongmei Ru, Leisheng |
author_sort | Ma, Yanzhuo |
collection | PubMed |
description | BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) is crucial in cardiac injury. Apolipoprotein-J (ApoJ) contributes to antiapoptotic effects in the heart. We aimed to evaluate the protective effects of ApoJ against ox-LDL cytotoxicity in Neonatal rat ventricular cells (NRVCs). METHODS AND RESULTS: NRVCs were damaged by exposure to ox-LDL, as shown by increased caspase-3/7 activity, enhanced caspase-3 expression, and decreased cell viability. ApoJ overexpression, using an adenovirus vector, significantly reduced ox-LDL-induced cell injury. ApoJ also prevented ox-LDL from augmenting reactive oxygen species (ROS) production, as demonstrated by elevated Nox2/gp91(phox) and P47 expression. Furthermore, ApoJ overexpression reduced CaMKIIδ expression elicited by ox-LDL in cultured NRVCs. Upregulating CaMKIIδ activity, mediated by ox-LDL, was significantly inhibited by ApoJ overexpression. A CaMKIIδ inhibitor, KN93, prevented ApoJ’s protective effect against ox-LDL cytotoxicity. A ROS scavenger, Mn (III)meso-tetrakis (4-benzoic acid) porphyrin (Mn (III)TBAP), also attenuated CaMKIIδ’s increased expression and activity, induced by ox-LDL, and showed similar results to ApoJ by attenuating ox-LDL-induced cell damage, as ApoJ did. CONCLUSIONS: ApoJ confers cytoprotection to NRVCs against ox-LDL cytotoxicity through the ROS-CaMKII pathways. |
format | Online Article Text |
id | pubmed-6530009 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65300092019-05-28 Apolipoprotein-J blocks increased cell injury elicited by ox-LDL via inhibiting ROS-CaMKII pathway Ma, Yanzhuo Gong, Zhi Nan, Kai Qi, Shuying Chen, Yu Ding, Chao Wang, Dongmei Ru, Leisheng Lipids Health Dis Research BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) is crucial in cardiac injury. Apolipoprotein-J (ApoJ) contributes to antiapoptotic effects in the heart. We aimed to evaluate the protective effects of ApoJ against ox-LDL cytotoxicity in Neonatal rat ventricular cells (NRVCs). METHODS AND RESULTS: NRVCs were damaged by exposure to ox-LDL, as shown by increased caspase-3/7 activity, enhanced caspase-3 expression, and decreased cell viability. ApoJ overexpression, using an adenovirus vector, significantly reduced ox-LDL-induced cell injury. ApoJ also prevented ox-LDL from augmenting reactive oxygen species (ROS) production, as demonstrated by elevated Nox2/gp91(phox) and P47 expression. Furthermore, ApoJ overexpression reduced CaMKIIδ expression elicited by ox-LDL in cultured NRVCs. Upregulating CaMKIIδ activity, mediated by ox-LDL, was significantly inhibited by ApoJ overexpression. A CaMKIIδ inhibitor, KN93, prevented ApoJ’s protective effect against ox-LDL cytotoxicity. A ROS scavenger, Mn (III)meso-tetrakis (4-benzoic acid) porphyrin (Mn (III)TBAP), also attenuated CaMKIIδ’s increased expression and activity, induced by ox-LDL, and showed similar results to ApoJ by attenuating ox-LDL-induced cell damage, as ApoJ did. CONCLUSIONS: ApoJ confers cytoprotection to NRVCs against ox-LDL cytotoxicity through the ROS-CaMKII pathways. BioMed Central 2019-05-22 /pmc/articles/PMC6530009/ /pubmed/31113434 http://dx.doi.org/10.1186/s12944-019-1066-8 Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Ma, Yanzhuo Gong, Zhi Nan, Kai Qi, Shuying Chen, Yu Ding, Chao Wang, Dongmei Ru, Leisheng Apolipoprotein-J blocks increased cell injury elicited by ox-LDL via inhibiting ROS-CaMKII pathway |
title | Apolipoprotein-J blocks increased cell injury elicited by ox-LDL via inhibiting ROS-CaMKII pathway |
title_full | Apolipoprotein-J blocks increased cell injury elicited by ox-LDL via inhibiting ROS-CaMKII pathway |
title_fullStr | Apolipoprotein-J blocks increased cell injury elicited by ox-LDL via inhibiting ROS-CaMKII pathway |
title_full_unstemmed | Apolipoprotein-J blocks increased cell injury elicited by ox-LDL via inhibiting ROS-CaMKII pathway |
title_short | Apolipoprotein-J blocks increased cell injury elicited by ox-LDL via inhibiting ROS-CaMKII pathway |
title_sort | apolipoprotein-j blocks increased cell injury elicited by ox-ldl via inhibiting ros-camkii pathway |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530009/ https://www.ncbi.nlm.nih.gov/pubmed/31113434 http://dx.doi.org/10.1186/s12944-019-1066-8 |
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