Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

PNAS 99 (2): 949-954

Copyright © 2002 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / MEDICAL SCIENCES

Tumor 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

Franky Van Herreweghe*, Jianqiang Mao{dagger}, Frank W. R. Chaplen{ddagger}, Johan Grooten{dagger}, Kris Gevaert*, Joël Vandekerckhove*, and Katia Vancompernolle*,{dagger},§

Departments of *Medical Protein Research and {dagger}Molecular Biology, Ghent University and Flanders Interuniversity Institute for Biotechnology, K. L. Ledeganckstraat 35, B-9000 Ghent, Belgium; and {ddagger}Department of Bioengineering, Oregon State University, 116 Gilmore Hall, Corvallis, OR 97331

Received for publication August 20, 2001.

Abstract: 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.


§ To whom reprint requests should be addressed at the present address: Department of Medical Protein Research, Albert Baertsoenkaai 3, 9000 Ghent, Belgium. E-mail: katia.vancompernolle{at}rug.ac.be.

Edited by Anthony Cerami, The Kenneth S. Warren Institute, Tarrytown, NY, and approved October 31, 2001

This paper was submitted directly (Track II) to the PNAS office.

Kim, Y. H. & Kim, S. S. (2001) Cancer Detect. Prev. 24, Suppl. 1 (abstr.).


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Mitochondrial Control of Cellular Life, Stress, and Death.
L. Galluzzi, O. Kepp, C. Trojel-Hansen, and G. Kroemer (2012)
Circ. Res. 111, 1198-1207
   Abstract »    Full Text »    PDF »
The Role of the Kinases RIP1 and RIP3 in TNF-Induced Necrosis.
P. Vandenabeele, W. Declercq, F. Van Herreweghe, and T. Vanden Berghe (2010)
Science Signaling 3, re4
   Abstract »    Full Text »    PDF »
Glyoxalase I overexpression ameliorates renal ischemia-reperfusion injury in rats.
T. Kumagai, M. Nangaku, I. Kojima, R. Nagai, J. R. Ingelfinger, T. Miyata, T. Fujita, and R. Inagi (2009)
Am J Physiol Renal Physiol 296, F912-F921
   Abstract »    Full Text »    PDF »
High Glucose Increases Angiopoietin-2 Transcription in Microvascular Endothelial Cells through Methylglyoxal Modification of mSin3A.
D. Yao, T. Taguchi, T. Matsumura, R. Pestell, D. Edelstein, I. Giardino, G. Suske, N. Rabbani, P. J. Thornalley, V. P. Sarthy, et al. (2007)
J. Biol. Chem. 282, 31038-31045
   Abstract »    Full Text »    PDF »
Proteomic analysis defines altered cellular redox pathways and advanced glycation end-product metabolism in glomeruli of db/db diabetic mice.
M. T. Barati, M. L. Merchant, A. B. Kain, A. W. Jevans, K. R. McLeish, and J. B. Klein (2007)
Am J Physiol Renal Physiol 293, F1157-F1165
   Abstract »    Full Text »    PDF »
Phosphoproteomic identification of targets of the Arabidopsis sucrose nonfermenting-like kinase SnRK2.8 reveals a connection to metabolic processes.
R. Shin, S. Alvarez, A. Y. Burch, J. M. Jez, and D. P. Schachtman (2007)
PNAS 104, 6460-6465
   Abstract »    Full Text »    PDF »
CpG Immunomer DNA Enhances Antisense Protein Kinase A RI{alpha} Inhibition of Multidrug-Resistant Colon Carcinoma Growth in Nude Mice: Molecular Basis for Combinatorial Therapy.
M. V. Nesterova, N. R. Johnson, T. Stewart, S. Abrams, and Y. S. Cho-Chung (2005)
Clin. Cancer Res. 11, 5950-5955
   Abstract »    Full Text »    PDF »
Involvement of Protein Kinase A in Cannabinoid Receptor-Mediated Protection from Oxidative Neuronal Injury.
S. H. Kim, S. J. Won, X. O. Mao, K. Jin, and D. A. Greenberg (2005)
J. Pharmacol. Exp. Ther. 313, 88-94
   Abstract »    Full Text »    PDF »
The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway.
H.-Y. Lee, Y. Xu, Y. Huang, A. H. Ahn, G. W.J. Auburger, M. Pandolfo, H. Kwiecinski, D. A. Grimes, A. E. Lang, J. E. Nielsen, et al. (2004)
Hum. Mol. Genet. 13, 3161-3170
   Abstract »    Full Text »    PDF »
Role for glyoxalase I in Alzheimer's disease.
F. Chen, M. A. Wollmer, F. Hoerndli, G. Munch, B. Kuhla, E. I. Rogaev, M. Tsolaki, A. Papassotiropoulos, and J. Gotz (2004)
PNAS 101, 7687-7692
   Abstract »    Full Text »    PDF »
Rapid Suppression of Mitochondrial Permeability Transition by Methylglyoxal: ROLE OF REVERSIBLE ARGININE MODIFICATION.
O. Speer, S. Morkunaite-Haimi, J. Liobikas, M. Franck, L. Hensbo, M. D. Linder, P. K. J. Kinnunen, T. Wallimann, and O. Eriksson (2003)
J. Biol. Chem. 278, 34757-34763
   Abstract »    Full Text »    PDF »
Advanced Glycation End Product Precursors Impair Epidermal Growth Factor Receptor Signaling.
M. Portero-Otin, R. Pamplona, M. J. Bellmunt, M. C. Ruiz, J. Prat, R. Salvayre, and A. Negre-Salvayre (2002)
Diabetes 51, 1535-1542
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882