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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Nature Portfolio
2021-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-84590-2 |
| _version_ | 1818436066379563008 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T17:02:52Z |
| format | Article |
| id | doaj.art-59ea855269e1402ba1274c9595d7d826 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T17:02:52Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-59ea855269e1402ba1274c9595d7d8262022-12-21T22:53:48ZengNature PortfolioScientific Reports2045-23222021-03-0111111410.1038/s41598-021-84590-2Comprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieuAlberto Valdés0Francisco J. Lucio-Cazaña1María Castro-Puyana2Coral García-Pastor3Oliver Fiehn4María Luisa Marina5Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de AlcaláDepartamento de Biología de Sistemas, Universidad de AlcaláDepartamento de Química Analítica, Química Física e Ingeniería Química, Universidad de AlcaláDepartamento de Biología de Sistemas, Universidad de AlcaláWest Coast Metabolomics Center, UC DavisDepartamento de Química Analítica, Química Física e Ingeniería Química, Universidad de AlcaláAbstract 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.https://doi.org/10.1038/s41598-021-84590-2 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-84590-2 |
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