Oxidative stress activates transcription factor NF-kB-mediated protective signaling in primary rat neuronal cultures.
Activation of transcription factor nuclear factor-kappaB (NF-kappaB) can result in enhanced de novo synthesis of both proteins that confer protection and those that cause death. The present study was undertaken to clarify in primary neuronal cultures the consequences of the oxidative stress-induced activation of NF-kappaB and mediation of death or survival signals. The neuronal cultures were exposed to chemical ischemia (iodoacetic acid), followed by reperfusion (I/R insult). This insult injured the neurons, as manifested in a 7- to 10-fold increase in LDH release, and decreased the cellular content of IkappaBalpha by 55-65 %, indicating NF-kappaB activation. The antioxidants LY231617, melatonin, and sodium salicylate and the antioxidant and inhibitor of NF-kappaB activation pyrrolidine dithiocarbamate, protected the neurons against the insult and prevented the decrease in cellular IkappaBalpha content. In contrast, inhibition of NF-kappaB translocation by SN50 in both uninsulted and insulted neuronal cultures resulted in a 2.9- and 2.4-fold increase in LDH release, respectively. The results indicate that the insult-induced oxidative stress activates transcription factor NF-kappaB associated with induction of protection and suggest that constitutive activation of NF-kappaB under physiological conditions acts to protect the neurons against physiological injury.
Kratsovnik
Ella
E
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Bromberg
Yael
Y
Sperling
Oded
O
Zoref-Shani
Esther
E
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D007461:Iodoacetates / Q000494:pharmacology; D016328:NF-kappa B / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D015427:Reperfusion Injury; D015398:Signal Transduction / Q000502:physiology*
D000975:Antioxidants; D007461:Iodoacetates; D016328:NF-kappa B