TitleTumor necrosis factor-induced modulation of glyoxalase I activities through phosphorylation by PKA results in cell death and is accompanied by the formation of a specific methylglyoxal-derived AGE.
Publication TypeJournal Article
Year of Publication2002
AuthorsVan Herreweghe, F, Mao, J, Chaplen, FWR, Grooten, J, Gevaert, K, Vandekerckhove, J, Vancompernolle, K
JournalProc Natl Acad Sci U S A
Date Published2002 Jan 22
KeywordsAnimals, Cell Death, Cyclic AMP-Dependent Protein Kinases, Glycosylation End Products, Advanced, Lactoylglutathione Lyase, Mice, Phosphorylation, Pyruvaldehyde, Reactive Oxygen Species, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha

Tumor necrosis factor (TNF)-induced cell death in the fibrosarcoma cell line L929 is a caspase-independent process that is characterized by increased production of reactive oxygen species (ROS) in the mitochondria. To elucidate this ROS-dependent cell death pathway, a comparative study of the phosphoproteins present in TNF-treated and control cells was performed. Here we report that TNF induces an increased phosphorylation of glyoxalase I that is mediated by protein kinase A and required for cell death. We also show that TNF induces a substantial increase in intracellular levels of methylglyoxal (MG) that leads to the formation of a specific MG-derived advanced glycation end product and that this formation occurs as a consequence of increased ROS production. These data indicate that MG modification of proteins is a targeted process and that MG may thus function as a signal molecule during the regulation of cell death. Furthermore, we provide evidence that the TNF-induced phosphorylation of glyoxalase I is not involved in detoxification of MG by means of the glyoxalase system, but that phosphorylated glyoxalase I is on the pathway leading to the formation of a specific MG-derived advanced glycation end product.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID11792832
PubMed Central IDPMC117411