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Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages

Cobalt is one of the main components of metal hip prostheses and cobalt nanoparticles (CoNPs) produced from wear cause inflammation, bone lyses and cytotoxicity at high concentrations. Cobalt ions mimic hypoxia in the presence of normal oxygen levels, and activate hypoxic signalling by stabilising h...

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Autores principales: Francis, Wendy Rachel, Liu, Zhao, Owens, Sian E, Wang, Xiao, Xue, Huaming, Lord, Alex, Kanamarlapudi, Venkateswarlu, Xia, Zhidao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chinese Medical Multimedia Press Co., Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255782/
https://www.ncbi.nlm.nih.gov/pubmed/35836963
http://dx.doi.org/10.12336/biomatertransl.2021.02.004
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author Francis, Wendy Rachel
Liu, Zhao
Owens, Sian E
Wang, Xiao
Xue, Huaming
Lord, Alex
Kanamarlapudi, Venkateswarlu
Xia, Zhidao
author_facet Francis, Wendy Rachel
Liu, Zhao
Owens, Sian E
Wang, Xiao
Xue, Huaming
Lord, Alex
Kanamarlapudi, Venkateswarlu
Xia, Zhidao
author_sort Francis, Wendy Rachel
collection PubMed
description Cobalt is one of the main components of metal hip prostheses and cobalt nanoparticles (CoNPs) produced from wear cause inflammation, bone lyses and cytotoxicity at high concentrations. Cobalt ions mimic hypoxia in the presence of normal oxygen levels, and activate hypoxic signalling by stabilising hypoxia inducible transcription factor 1α (HIF1α). This study aimed to assess in vitro the functional role of HIF1α in CoNP induced cellular cytotoxicity. HIF1α, lysosomal pH, tumour necrosis factor α and interleukin 1β expression were analysed in THP-1 macrophages treated with CoNP (0, 10 and 100 μg/mL). HIF1α knock out assays were performed using small interfering RNA to assess the role of HIF1α in CoNP-induced cytotoxicity. Increasing CoNP concentration increased lysosomal activity and acidity in THP-1 macrophages. Higher doses of CoNP significantly reduced cell viability, stimulated caspase 3 activity and apoptosis. Reducing HIF1αactivity increased the pro-inflammatory activity of tumour necrosis factorαand interleukin 1β,but had no significant impact on cellular cytotoxicity. This suggests that whilst CoNP promotes cytotoxicity and cellular inflammation, the apoptotic mechanism is not dependent on HIF1α.
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spelling pubmed-92557822022-07-13 Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages Francis, Wendy Rachel Liu, Zhao Owens, Sian E Wang, Xiao Xue, Huaming Lord, Alex Kanamarlapudi, Venkateswarlu Xia, Zhidao Biomater Transl Research Article Cobalt is one of the main components of metal hip prostheses and cobalt nanoparticles (CoNPs) produced from wear cause inflammation, bone lyses and cytotoxicity at high concentrations. Cobalt ions mimic hypoxia in the presence of normal oxygen levels, and activate hypoxic signalling by stabilising hypoxia inducible transcription factor 1α (HIF1α). This study aimed to assess in vitro the functional role of HIF1α in CoNP induced cellular cytotoxicity. HIF1α, lysosomal pH, tumour necrosis factor α and interleukin 1β expression were analysed in THP-1 macrophages treated with CoNP (0, 10 and 100 μg/mL). HIF1α knock out assays were performed using small interfering RNA to assess the role of HIF1α in CoNP-induced cytotoxicity. Increasing CoNP concentration increased lysosomal activity and acidity in THP-1 macrophages. Higher doses of CoNP significantly reduced cell viability, stimulated caspase 3 activity and apoptosis. Reducing HIF1αactivity increased the pro-inflammatory activity of tumour necrosis factorαand interleukin 1β,but had no significant impact on cellular cytotoxicity. This suggests that whilst CoNP promotes cytotoxicity and cellular inflammation, the apoptotic mechanism is not dependent on HIF1α. Chinese Medical Multimedia Press Co., Ltd 2021-06-28 /pmc/articles/PMC9255782/ /pubmed/35836963 http://dx.doi.org/10.12336/biomatertransl.2021.02.004 Text en https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Research Article
Francis, Wendy Rachel
Liu, Zhao
Owens, Sian E
Wang, Xiao
Xue, Huaming
Lord, Alex
Kanamarlapudi, Venkateswarlu
Xia, Zhidao
Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
title Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
title_full Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
title_fullStr Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
title_full_unstemmed Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
title_short Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
title_sort role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human thp-1 macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255782/
https://www.ncbi.nlm.nih.gov/pubmed/35836963
http://dx.doi.org/10.12336/biomatertransl.2021.02.004
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