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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Tomin, T; Honeder, SE; Liesinger, L; Gremel, D; Retzl, B; Lindenmann, J; Brcic, L; Schittmayer, M; Birner-Gruenberger, R.
Increased antioxidative defense and reduced advanced glycation end-product formation by metabolic adaptation in non-small-cell-lung-cancer patients.
Nat Commun. 2025; 16(1):5157
Doi: 10.1038/s41467-025-60326-y
PubMed
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- Führende Autor*innen der Med Uni Graz
- Birner-Grünberger Ruth
- Schittmayer-Schantl Matthias
- Tomin Tamara
- Co-Autor*innen der Med Uni Graz
- Brcic Luka
- Honeder Sophie
- Liesinger Laura
- Lindenmann Jörg
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- Abstract:
- Reactive oxygen species can oxidatively modify enzymes to reroute metabolism according to tumor needs, rendering identification of oxidized proteins important for understanding neoplastic survival mechanisms. Thiol groups are most susceptible to oxidative modifications but challenging to analyze in clinical settings. We here describe the protein and small-molecular thiol oxidation landscape of 70 human lung tumors (and their paired healthy counter parts) and demonstrate that cancer adapts metabolism to increase glutathione synthesis to counteract oxidative stress. Glyoxalases, the key enzymes in the detoxification of methylglyoxal, a byproduct of glycolysis and precursor of advanced glycation end-products, are compromised by oxidation and downregulation. Despite decreased methylglyoxal detoxification capacity, cancers do not accumulate advanced glycation end-products. Since in vitro downregulation or inhibition of GAPDH upregulates glyoxalases, we propose that tumors reduce methylglyoxal by activating GAPDH.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Glycation End Products, Advanced - metabolism
- Carcinoma, Non-Small-Cell Lung - metabolism, pathology, genetics
- Lung Neoplasms - metabolism, pathology
- Pyruvaldehyde - metabolism
- Lactoylglutathione Lyase - metabolism, genetics
- Oxidative Stress - administration & dosage
- Glutathione - metabolism
- Male - administration & dosage
- Oxidation-Reduction - administration & dosage
- Female - administration & dosage
- Reactive Oxygen Species - metabolism
- Antioxidants - metabolism
- Middle Aged - administration & dosage
- Aged - administration & dosage
- Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) - metabolism
- Sulfhydryl Compounds - metabolism
- Cell Line, Tumor - administration & dosage
- Glycolysis - administration & dosage