Molecular cell, 2015-08, Vol.59 (3), p.359-371
2015
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- Autor(en) / Beteiligte
- Titel
- Acute Activation of Oxidative Pentose Phosphate Pathway as First-Line Response to Oxidative Stress in Human Skin Cells
- Ist Teil von
- Molecular cell, 2015-08, Vol.59 (3), p.359-371
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 13C 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. [Display omitted] •Oxidants induce rerouting of glucose flux into oxidative PPP within seconds•Initial rerouting is independent of GADPH or PKM2 inhibition•Multiple cycling of carbon molecules in PPP potentially amplifies NADPH production•PPP activation might be involved in resistance against ROS-based cancer therapies The human skin is continuously exposed to oxidative stress induced by UV irradiation. Kuehne and Emmert et al. report how skin cells reroute glucose flux into the oxidative pentose phosphate pathway as a first-line defense to increase NADPH production, which is essential to prevent oxidative damage.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1097-2765eISSN: 1097-4164DOI: 10.1016/j.molcel.2015.06.017Titel-ID: cdi_crossref_primary_10_1016_j_molcel_2015_06_017
- Format
- –
- Schlagworte
- Carrier Proteins - metabolism, Cells, Cultured, Fibroblasts - cytology, Fibroblasts - drug effects, Fibroblasts - metabolism, Fibroblasts - radiation effects, Gene Expression Regulation - drug effects, Gene Expression Regulation - radiation effects, Humans, Hydrogen Peroxide - pharmacology, Infant, Newborn, Keratinocytes - cytology, Keratinocytes - drug effects, Keratinocytes - metabolism, Keratinocytes - radiation effects, Membrane Proteins - metabolism, Metabolomics - methods, NADP - metabolism, Oxidative Stress - drug effects, Pentose Phosphate Pathway - drug effects, Pentose Phosphate Pathway - radiation effects, Reactive Oxygen Species - metabolism, Thyroid Hormone-Binding Proteins, Thyroid Hormones - metabolism