Chonnam Med J.
2003 Sep;39(3):149-155.
Effects of Different Kinds of Oxidants on NF-kappaB Activity in Cortical Cell Cultures
- Affiliations
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- 1Department of Pharmacology, Chonnam National University Medical School, Gwangju, Korea. ckkim@chonnam.ac.kr
- 2Department of Neurosurgery, Chonnam National University Medical School, Gwangju, Korea.
- 3Department of Anatomy, Chonnam National University Medical School, Gwangju, Korea.
- 4Chonnam National University Research Institute of Medical Sciences, Gwangju, Korea.
Abstract
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In order to delineate the interrelationship between oxidative neuronal injury and changes in NF-kappaB activity, the effects of trolox (an antioxidant), cycloheximde (CHX, a protein synthesis inhibitor), brain-derived neurotrophic factor (BDNF) or pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-kappaB activation) on the neuronal death and the changes in NF-kappaB binding activity induced by 2,2'-azobis(2-amidinopropane) 2HCl (AAPH, 1 mM), 2,2'-azobis(2,4-dimethyl-valeronitrile) (AMVN, 300 microM) or sodium nitroprusside (SNP, 1 microM) were examined in mouse mixed cortical cultures. Co-treatment with trolox (100 microM) markedly attenuated the neuronal deaths induced by all three oxidants. Co-treatment with CHX (0.1 microgram/ml) had no effect on the oxidant-induced neuronal deaths, whereas pre-treatment with CHX for 2 hr significantly attenuated the neuronal deaths. Pre-treatment with BDNF (100 ng/ml) potentiated the AAPH- or AMVN-induced neuronal death. Co-treatment with PDTC (50 microM) did not affect the SNP-induced neuronal death. The NF-kappaB binding activity was relatively high in nuclear extracts of cells exposed to the vehicles, while it was decreased in nuclear extracts of cells exposed for 1 hr to all three oxidants in this study. The decrease of NF-kappaB binding activity by AAPH was partially restored by co-treatment with trolox or pre-treatment with BDNF, while CHX treatment did not affect it. The AMVN-induced decrease was augmented by pretreatment with CHX, while it was not affected by the treatment with trolox or BDNF. The SNP-induced decrease was augmented by co-treatment with trolox, whereas it was not affected by the treatment with CHX or PDTC. These results suggest that changes of NF-kappaB binding activity have no inter-relationship with the oxidative neuronal deaths induced by the three oxidants employed in this study.