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Acute Activation of Oxidative Pentose Phosphate Pathway as First-Line Response to Oxidative Stress in Human Skin Cells
Open accessAbstract
Integrity of human skin is endangered by exposure to UV irradiation and chemical stressors, which can provoke a toxic production of reactive oxygen species (ROS) and oxidative damage. Since oxidation of proteins and metabolites occurs virtually instantaneously, immediate cellular countermeasures are pivotal to mitigate the negative implications of acute oxidative stress. We investigated the short-term metabolic response in human skin fibroblasts and keratinocytes to H2O2 and UV exposure. In time-resolved metabolomics experiments, we observed that within seconds after stress induction, glucose catabolism is routed to the oxidative pentose phosphate pathway (PPP) and nucleotide synthesis independent of previously postulated blocks in glycolysis (i.e., of GAPDH or PKM2). Through ultra-short (13)C labeling experiments, we provide evidence for multiple cycling of carbon backbones in the oxidative PPP, potentially maximizing NADPH reduction. The identified metabolic rerouting in oxidative and non-oxidative PPP has important physiological roles in stabilization of the redox balance and ROS clearance.
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Cites
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Hayes, J. D., Dinkova-Kostova, A. T., & Tew, K. D. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.06.001 · Cited by 2,654
Understanding the Intersections between Metabolism and Cancer Biology
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The pentose phosphate pathway in health and disease
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Interplay between oxidant species and energy metabolism
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The Influence of Metabolism on Drug Response in Cancer
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Metadata
- Authors
- Kuehne, A., Emmert, H., Soehle, J., Winnefeld, M., Fischer, F., Wenck, H., Gallinat, S., Terstegen, L., Lucius, R., Hildebrand, J., & Zamboni, N.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 59
- Issue
- 3
- Pages
- 359-371
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1707133078
- Cited by
- 383
- References
- 50
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kuehne, A., Emmert, H., Soehle, J., Winnefeld, M., Fischer, F., Wenck, H., Gallinat, S., Terstegen, L., Lucius, R., Hildebrand, J., & Zamboni, N. (2015). Acute Activation of Oxidative Pentose Phosphate Pathway as First-Line Response to Oxidative Stress in Human Skin Cells. Molecular Cell. https://doi.org/10.1016/j.molcel.2015.06.017
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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