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Creatine enhances survival of glutamate‐treated neuronal/glial cells, modulates Ras/NF‐κB signaling, and increases the generation of reactive oxygen species
Author(s) -
Juravleva Elena,
Barbakadze Tamar,
Mikeladze David,
Kekelidze Téa
Publication year - 2004
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20291
Subject(s) - creatine , neuroprotection , reactive oxygen species , glutamate receptor , microbiology and biotechnology , biology , programmed cell death , signal transduction , biochemistry , pharmacology , apoptosis , receptor
The protective effects of creatine against glutamate cytotoxicity have been demonstrated in neuronal cells and animal models of neurodegenerative diseases. The mechanisms underlying creatine neuroprotection against glutamate‐induced cell death are understood poorly. For the first time, we demonstrate a correlation between the protective effect of creatine and the modulation of Ras‐mediated redox‐dependent signaling pathways, which involve nuclear factor κB (NF‐κB) and reactive oxygen species (ROS). In primary cerebrocortical cultures of mixed neurons and glia, creatine significantly reduced glutamate‐induced cell death. The increase in cell survival was accompanied by increased generation of oxygen radicals and decreased levels of farnesylated Ras and IκB, an inhibitor of NF‐κB. Non‐farnesylated Ras and ROS‐dependent activation of NF‐κB have been shown to promote neuronal survival. Our data suggest that creatine may enhance survival signaling via activation of the Ras/NF‐κB system. Possible mechanisms underlying the protective effect of creatine are discussed, including normalization of cellular GTP levels. © 2004 Wiley‐Liss, Inc.