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

Wendy Francis Orcid Logo, Sian-eleri Owens Orcid Logo, Venkat Kanamarlapudi Orcid Logo, Zhidao Xia Orcid Logo

Biomaterials Translational, Volume: 2, Issue: 2, Pages: 143 - 150

Swansea University Authors: Wendy Francis Orcid Logo, Sian-eleri Owens Orcid Logo, Venkat Kanamarlapudi Orcid Logo, Zhidao Xia Orcid Logo

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DOI (Published version): 10.12336/biomatertransl.2021.02.004

Abstract

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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Published in: Biomaterials Translational
ISSN: 2096-112X
Published: 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa57975
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spelling 2022-10-27T11:24:15.0229453 v2 57975 2021-09-20 Role of hypoxia inducible factor 1alpha in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages f0ec2a3fdae1cf112579d579afbe9813 0000-0002-7952-2770 Wendy Francis Wendy Francis true false 721deb4604d122019244cfdf08820cbe 0000-0003-1806-5235 Sian-eleri Owens Sian-eleri Owens true false 63741801137148abfa4c00cd547dcdfa 0000-0002-8739-1483 Venkat Kanamarlapudi Venkat Kanamarlapudi true false c9307abfed1b43987a19da0c0e30d7a4 0000-0002-2047-7282 Zhidao Xia Zhidao Xia true false 2021-09-20 BMS 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 HIF1α activity increased the pro-inflammatory activity of tumour necrosis factor α and 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. Journal Article Biomaterials Translational 2 2 143 150 2096-112X cobalt nanoparticle, cytotoxicity, hypoxia inducible factor, macrophages, TNFα 28 6 2021 2021-06-28 10.12336/biomatertransl.2021.02.004 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2022-10-27T11:24:15.0229453 2021-09-20T12:18:18.2400896 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Wendy Francis 0000-0002-7952-2770 1 Sian-eleri Owens 0000-0003-1806-5235 2 Venkat Kanamarlapudi 0000-0002-8739-1483 3 Zhidao Xia 0000-0002-2047-7282 4 57975__21245__21249d76485d4a44bc13dcf6e6c1f47a.pdf 57975.pdf 2021-10-20T15:32:56.5996863 Output 1251589 application/pdf Version of Record true Released under the terms of a Creative Commons Attribution-NonCommercial-NoDerivs License (CC BY-NC-ND 4.0) true eng https://creativecommons.org/licenses/by-nc-nd/4.0/
title Role of hypoxia inducible factor 1alpha in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
spellingShingle Role of hypoxia inducible factor 1alpha in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
Wendy Francis
Sian-eleri Owens
Venkat Kanamarlapudi
Zhidao Xia
title_short Role of hypoxia inducible factor 1alpha in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
title_full Role of hypoxia inducible factor 1alpha in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
title_fullStr Role of hypoxia inducible factor 1alpha in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
title_full_unstemmed Role of hypoxia inducible factor 1alpha in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
title_sort Role of hypoxia inducible factor 1alpha in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages
author_id_str_mv f0ec2a3fdae1cf112579d579afbe9813
721deb4604d122019244cfdf08820cbe
63741801137148abfa4c00cd547dcdfa
c9307abfed1b43987a19da0c0e30d7a4
author_id_fullname_str_mv f0ec2a3fdae1cf112579d579afbe9813_***_Wendy Francis
721deb4604d122019244cfdf08820cbe_***_Sian-eleri Owens
63741801137148abfa4c00cd547dcdfa_***_Venkat Kanamarlapudi
c9307abfed1b43987a19da0c0e30d7a4_***_Zhidao Xia
author Wendy Francis
Sian-eleri Owens
Venkat Kanamarlapudi
Zhidao Xia
author2 Wendy Francis
Sian-eleri Owens
Venkat Kanamarlapudi
Zhidao Xia
format Journal article
container_title Biomaterials Translational
container_volume 2
container_issue 2
container_start_page 143
publishDate 2021
institution Swansea University
issn 2096-112X
doi_str_mv 10.12336/biomatertransl.2021.02.004
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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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 HIF1α activity increased the pro-inflammatory activity of tumour necrosis factor α and 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.
published_date 2021-06-28T04:14:07Z
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score 11.037581

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