title: Acute Activation of Oxidative Pentose Phosphate Pathway as First-Line Response to Oxidative Stress in Human Skin Cells.
abstract: 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.
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, 8093 Zurich, Switzerland; PhD Program Systems Biology, Life Science Zurich Graduate School, 8093 Zurich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kuehne
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253 Germany.
authors.forename: Hila
authors.initials: H
authors.lastname: Emmert
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253 Germany.
authors.forename: Joern
authors.initials: J
authors.lastname: Soehle
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253 Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Winnefeld
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253 Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Fischer
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253 Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Wenck
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253 Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gallinat
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253 Germany.
authors.forename: Lara
authors.initials: L
authors.lastname: Terstegen
authors.affiliation: Christian Albrecht University Kiel, Department of Anatomy, Otto-Hahn-Platz 8, 24118 Kiel, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Lucius
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253 Germany. Electronic address: Janosch.Hildebrand@Beiersdorf.com.
authors.forename: Janosch
authors.initials: J
authors.lastname: Hildebrand
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, 8093 Zurich, Switzerland. Electronic address: zamboni@imsb.biol.ethz.ch.
authors.forename: Nicola
authors.initials: N
authors.lastname: Zamboni
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D008565:Membrane Proteins / Q000378:metabolism*; D055432:Metabolomics / Q000379:methods; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010427:Pentose Phosphate Pathway / Q000187:drug effects* / Q000528:radiation effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D006861:Hydrogen Peroxide; D008565:Membrane Proteins; D009249:NADP; D017382:Reactive Oxygen Species; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins