Chonnam Med J.
2001 Dec;37(4):377-382.
Interrelationship between Oxidative Neuronal Injury Induced by Iron or Buthionine Sulfoximine and NF-kappaB Activity in Mixed Cortical Cultures
- Affiliations
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- 1Departments of Pharmacology, Chonnam National University Medical School, Chonnam National University Research Institute of Medical Sciences, Kwangju, Korea.
- 2Departments of Anatomy, Chonnam National University Medical School, Chonnam National University Research Institute of Medical Sciences, Kwangju, Korea.
Abstract
- In order to delineate the interrelationship between oxidative neuronal injury and changes in NF-kappaB activity, the effects of trolox (a vitamin E analog antioxidant), cycloheximde (CHX, a protein synthesis inhibitor) or pyrrolidine dithiocarbamate (PDTC, a inhibitor of NF-kappaB activation) on the neuronal death and the changes in NF-kappaB binding activity induced by FeCl2 or buthionine sulfoximine (BSO) were examined in mouse mixed cortical cultures. The neuronal death induced by 20 micrometer FeCl2 was almost abolished by co-treatment with trolox (100 micrometer), but markedly potentiated by co-treatment with CHX (1 microgram/ml) or PDTC (50 micrometer). The neuronal death induced by 1 mM BSO was almost abolished by co-treatment with trolox or CHX, but not affected by co-treatment with PDTC (50 micrometer). NF-kappaB binding activity was induced in nuclear extract of cells exposed for 2 hr to 20 micrometer FeCl2 or 1 mM BSO. Co-treatment with CHX potentiated the induction of NF-kappaB binding activity by the exposure to 20 micrometer FeCl2 for 2 hr, but prevented the induction of NF-kappaB binding activity by 1 mM BSO. Trolox or PDTC prevented the induction of NF-kappaB binding activity by FeCl2 or BSO. These results demonstrated that the changes of NF-kappaB binding activity took part in the effects of CHX or trolox on the oxidative neuronal death as well as the oxidative neuronal death induced by FeCl2 or BSO.