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Neutrophil Gelatinase-Associated Lipocalin2 Exaggerates Cardiomyocyte Hypoxia Injury by Inhibiting Integrin β3 Signaling
BACKGROUND: The neutrophil inflammatory protein, lipocalin-2 (NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, the specific role of NGAL in cardiac hypoxia injury is unclear. This study aimed to elucidate the functional role of NGAL in cardiomyocyte hypoxi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scientific Literature, Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668495/ https://www.ncbi.nlm.nih.gov/pubmed/31327865 http://dx.doi.org/10.12659/MSM.915108 |
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author | Gu, Yang Geng, Jin Xu, Zhuo Chen, Yu Zhang, Xi-Wen |
author_facet | Gu, Yang Geng, Jin Xu, Zhuo Chen, Yu Zhang, Xi-Wen |
author_sort | Gu, Yang |
collection | PubMed |
description | BACKGROUND: The neutrophil inflammatory protein, lipocalin-2 (NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, the specific role of NGAL in cardiac hypoxia injury is unclear. This study aimed to elucidate the functional role of NGAL in cardiomyocyte hypoxia injury. MATERIAL/METHODS: Neonatal rat cardiomyocytes were transfected with adenovirus [(Ad-NGAL] to overexpress human-NGAL and then were exposed to hypoxia for 24 h to establish a hypoxia model. Cell inflammation was detected by RT-PCT and ELISA assay. Cell apoptosis was detected by TUNEL assay. Oxidative stress was also detected by commercial kits. RESULTS: An increased inflammatory response, apoptosis, and augmented oxidative stress were observed after exposure to hypoxia, while NGAL overexpression in cells increased the expression and release of inflammatory cytokines. NGAL overexpression also increased the number of apoptotic cells and the imbalance of Bax/Bcl-2 protein expression. Moreover, NGAL overexpression increased the levels of reactive oxygen species and oxidase activity, but reduced anti-oxidase activity. Mechanistically, we found that NGAL decreased the expression of integrin β3, but not the expression of integrin avβ3 and avβ5, thus inhibiting the downstream protein AKT. When we used the constitutively activated AKT overexpression adenovirus to activate AKT, the deteriorated phenotype by NGAL was counteracted. CONCLUSIONS: NGAL can directly affect cardiomyocytes and cause cardiomyocyte deteriorated hypoxia injury through inhibiting integrin β3 signaling. |
format | Online Article Text |
id | pubmed-6668495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | International Scientific Literature, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66684952019-08-16 Neutrophil Gelatinase-Associated Lipocalin2 Exaggerates Cardiomyocyte Hypoxia Injury by Inhibiting Integrin β3 Signaling Gu, Yang Geng, Jin Xu, Zhuo Chen, Yu Zhang, Xi-Wen Med Sci Monit Lab/In Vitro Research BACKGROUND: The neutrophil inflammatory protein, lipocalin-2 (NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, the specific role of NGAL in cardiac hypoxia injury is unclear. This study aimed to elucidate the functional role of NGAL in cardiomyocyte hypoxia injury. MATERIAL/METHODS: Neonatal rat cardiomyocytes were transfected with adenovirus [(Ad-NGAL] to overexpress human-NGAL and then were exposed to hypoxia for 24 h to establish a hypoxia model. Cell inflammation was detected by RT-PCT and ELISA assay. Cell apoptosis was detected by TUNEL assay. Oxidative stress was also detected by commercial kits. RESULTS: An increased inflammatory response, apoptosis, and augmented oxidative stress were observed after exposure to hypoxia, while NGAL overexpression in cells increased the expression and release of inflammatory cytokines. NGAL overexpression also increased the number of apoptotic cells and the imbalance of Bax/Bcl-2 protein expression. Moreover, NGAL overexpression increased the levels of reactive oxygen species and oxidase activity, but reduced anti-oxidase activity. Mechanistically, we found that NGAL decreased the expression of integrin β3, but not the expression of integrin avβ3 and avβ5, thus inhibiting the downstream protein AKT. When we used the constitutively activated AKT overexpression adenovirus to activate AKT, the deteriorated phenotype by NGAL was counteracted. CONCLUSIONS: NGAL can directly affect cardiomyocytes and cause cardiomyocyte deteriorated hypoxia injury through inhibiting integrin β3 signaling. International Scientific Literature, Inc. 2019-07-22 /pmc/articles/PMC6668495/ /pubmed/31327865 http://dx.doi.org/10.12659/MSM.915108 Text en © Med Sci Monit, 2019 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) ) |
spellingShingle | Lab/In Vitro Research Gu, Yang Geng, Jin Xu, Zhuo Chen, Yu Zhang, Xi-Wen Neutrophil Gelatinase-Associated Lipocalin2 Exaggerates Cardiomyocyte Hypoxia Injury by Inhibiting Integrin β3 Signaling |
title | Neutrophil Gelatinase-Associated Lipocalin2 Exaggerates Cardiomyocyte Hypoxia Injury by Inhibiting Integrin β3 Signaling |
title_full | Neutrophil Gelatinase-Associated Lipocalin2 Exaggerates Cardiomyocyte Hypoxia Injury by Inhibiting Integrin β3 Signaling |
title_fullStr | Neutrophil Gelatinase-Associated Lipocalin2 Exaggerates Cardiomyocyte Hypoxia Injury by Inhibiting Integrin β3 Signaling |
title_full_unstemmed | Neutrophil Gelatinase-Associated Lipocalin2 Exaggerates Cardiomyocyte Hypoxia Injury by Inhibiting Integrin β3 Signaling |
title_short | Neutrophil Gelatinase-Associated Lipocalin2 Exaggerates Cardiomyocyte Hypoxia Injury by Inhibiting Integrin β3 Signaling |
title_sort | neutrophil gelatinase-associated lipocalin2 exaggerates cardiomyocyte hypoxia injury by inhibiting integrin β3 signaling |
topic | Lab/In Vitro Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668495/ https://www.ncbi.nlm.nih.gov/pubmed/31327865 http://dx.doi.org/10.12659/MSM.915108 |
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