Abstract
Oxygen deficiency in cells, tissues, and organs can not only prevent the proper development of biological functions but it can also lead to several diseases and disorders. In this sense, the kidney deserves special attention since hypoxia can be considered an important factor in the pathophysiology of both acute kidney injury and chronic kidney disease. To provide better knowledge to unveil the molecular mechanisms involved, new studies are necessary. In this sense, this work aims to study, for the first time, an in vitro model of hypoxia-induced metabolic alterations in human proximal tubular HK-2 cells because renal proximal tubules are particularly susceptible to hypoxia. Different groups of cells, cultivated under control and hypoxia conditions at 0.5, 5, 24, and 48 h, were investigated using untargeted metabolomic approaches based on reversed-phase liquid chromatography–mass spectrometry. Both intracellular and extracellular fluids were studied to obtain a large metabolite coverage. On the other hand, multivariate and univariate analyses were carried out to find the differences among the cell groups and to select the most relevant variables. The molecular features identified as affected metabolites were mainly amino acids and Amadori compounds. Insights about their biological relevance are also provided.
Highlights
Licensee MDPI, Basel, Switzerland.Oxygen, one of the most abundant elements in the atmosphere, is essential for carrying out the cellular function successfully
To select the To select the hypoxia time that is more suitable for inducing sufficient metabolic changes hypoxia time that is more suitable for inducing sufficient metabolic changes in HK-2 cells, in HK-2 cells, the hypoxia-inducible factors (HIFs)-1α wasdifferent assayedtime over different time
The current study has identified several potentially relevant metabolic changes induced by hypoxia in the intracellular or extracellular fluids of HK-2 cells, which are discussed below
Summary
One of the most abundant elements in the atmosphere, is essential for carrying out the cellular function successfully. Maintaining an adequate oxygen level is a key factor. Hypoxia results in hyperventilation and sympathetic activation in mammals, increasing the uptake and distribution of oxygen to cells and tissues within a few seconds. The generation of new blood vessels and the synthesis of erythrocytes and nonaerobic ATP increase if the hypoxia occurs for hours or days [1]. To carry out these adaptations, an extensive genetic program is necessary, which is possible thanks to the hypoxia-inducible factors (HIFs) [3]. HIF-1α is ubiquitously expressed and is found in most renal epithelial cells, including proximal tubular cells [3]
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