Neurotoxicology. 2005 May 12; [Epub ahead of print] Links
Antioxidant Treatment Inhibited Glutamate-Evoked NF-kappaB Activation in Primary Astroglial Cell Cultures.
Caccamo D, Campisi A, Curro M, Bramanti V, Tringali M, Volti GL, Vanella A, Ientile R.
Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Via Consolare Valeria, Policlinico Universitario, 98125 Messina, Italy.
In glial cells, glutamate exposure causes alterations in cell redox status, mainly mediated by glutathione depletion and reactive oxygen species generation. These effects finally lead to astrocyte dysfunction which contributes to the pathogenesis of several neurological disorders. This study was aimed to investigate the involvement of the NF-kappaB pathway in oxidative stress induced by glutamate exposure in primary cultures of astrocytes. Further, we evaluated the power of the antioxidants genistein (0.1-10muM) and IRFI 016 (20-80muM), a synthetic tocopherol analogue, compared with glutathione ethyl ester (10-50muM) and cysteamine-HCl (100-500muM), to antagonize the effects elicited by glutamate (500muM). Alterations of cell redox status were reduced, in a dose-dependent way, by antioxidants; in particular, 80muM IRFI 016 and
10muM genistein almost completely restored glutathione basal levels and significantly diminished ROS production, as well as 100muM glutathione ethyl ester. These antioxidant effects were stronger than those caused by 500muM cysteamine-HCl. Further, glutamate promoted the up-regulation of p50 and p65 NF-kappaB subunits and their nuclear translocation, as revealed by Western blot analysis and electrophoretic mobility shift assay of both subunits. The activation of p50 and p65 NF-kappaB subunits induced by glutamate exposure was significantly reduced by IRFI 016, acting in a dose-dependent manner. Altogether, these data confirm that the NF-kappaB pathway is involved in cell response to oxidative stress induced by glutamate injury in primary astrocyte cultures, and suggest that the use of antioxidants, such as IRFI 016, may be a helpful pharmacological strategy for neuroprotection.PMID: 15894376 [PubMed - as supplied by publisher]
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