Comprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieu

Abstract Diabetic nephropathy (DN) is the leading cause of chronic kidney disease. Although hyperglycaemia has been determined as the most important risk factor, hypoxia also plays a relevant role in the development of this disease. In this work, a comprehensive metabolomic study of the response of...

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Autores principales:	Alberto Valdés, Francisco J. Lucio-Cazaña, María Castro-Puyana, Coral García-Pastor, Oliver Fiehn, María Luisa Marina
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/59ea855269e1402ba1274c9595d7d826
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spelling	oai:doaj.org-article:59ea855269e1402ba1274c9595d7d8262021-12-02T13:35:03ZComprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieu10.1038/s41598-021-84590-22045-2322https://doaj.org/article/59ea855269e1402ba1274c9595d7d8262021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84590-2https://doaj.org/toc/2045-2322Abstract Diabetic nephropathy (DN) is the leading cause of chronic kidney disease. Although hyperglycaemia has been determined as the most important risk factor, hypoxia also plays a relevant role in the development of this disease. In this work, a comprehensive metabolomic study of the response of HK-2 cells, a human cell line derived from normal proximal tubular epithelial cells, to hyperglycemic, hypoxic diabetic-like milieu has been performed. Cells simultaneously exposed to high glucose (25 mM) and hypoxia (1% O2) were compared to cells in control conditions (5.5 mM glucose/18.6% O2) at 48 h. The combination of advanced metabolomic platforms (GC-TOF MS, HILIC- and CSH-QExactive MS/MS), freely available metabolite annotation tools, novel databases and libraries, and stringent cut-off filters allowed the annotation of 733 metabolites intracellularly and 290 compounds in the extracellular medium. Advanced bioinformatics and statistical tools demonstrated that several pathways were significantly altered, including carbohydrate and pentose phosphate pathways, as well as arginine and proline metabolism. Other affected metabolites were found in purine and lipid metabolism, the protection against the osmotic stress and the prevention of the activation of the β-oxidation pathway. Overall, the effects of the combined exposure of HK-cells to high glucose and hypoxia are reasonably compatible with previous in vivo works.Alberto ValdésFrancisco J. Lucio-CazañaMaría Castro-PuyanaCoral García-PastorOliver FiehnMaría Luisa MarinaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alberto Valdés Francisco J. Lucio-Cazaña María Castro-Puyana Coral García-Pastor Oliver Fiehn María Luisa Marina Comprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieu
description	Abstract Diabetic nephropathy (DN) is the leading cause of chronic kidney disease. Although hyperglycaemia has been determined as the most important risk factor, hypoxia also plays a relevant role in the development of this disease. In this work, a comprehensive metabolomic study of the response of HK-2 cells, a human cell line derived from normal proximal tubular epithelial cells, to hyperglycemic, hypoxic diabetic-like milieu has been performed. Cells simultaneously exposed to high glucose (25 mM) and hypoxia (1% O2) were compared to cells in control conditions (5.5 mM glucose/18.6% O2) at 48 h. The combination of advanced metabolomic platforms (GC-TOF MS, HILIC- and CSH-QExactive MS/MS), freely available metabolite annotation tools, novel databases and libraries, and stringent cut-off filters allowed the annotation of 733 metabolites intracellularly and 290 compounds in the extracellular medium. Advanced bioinformatics and statistical tools demonstrated that several pathways were significantly altered, including carbohydrate and pentose phosphate pathways, as well as arginine and proline metabolism. Other affected metabolites were found in purine and lipid metabolism, the protection against the osmotic stress and the prevention of the activation of the β-oxidation pathway. Overall, the effects of the combined exposure of HK-cells to high glucose and hypoxia are reasonably compatible with previous in vivo works.
format	article
author	Alberto Valdés Francisco J. Lucio-Cazaña María Castro-Puyana Coral García-Pastor Oliver Fiehn María Luisa Marina
author_facet	Alberto Valdés Francisco J. Lucio-Cazaña María Castro-Puyana Coral García-Pastor Oliver Fiehn María Luisa Marina
author_sort	Alberto Valdés
title	Comprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieu
title_short	Comprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieu
title_full	Comprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieu
title_fullStr	Comprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieu
title_full_unstemmed	Comprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieu
title_sort	comprehensive metabolomic study of the response of hk-2 cells to hyperglycemic hypoxic diabetic-like milieu
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/59ea855269e1402ba1274c9595d7d826
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Comprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieu

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