Cerebral ischemia: gene activation, neuronal injury, and the protective role of antioxidants.
A large number of gene products appear after an ischemic insult making it difficult to decipher which genes are involved in tissue injury. Reactive oxygen species (ROS) can influence gene expression and have a role in the events that lead to neuronal death. In global cerebral ischemia the oxidative responsive transcription factor, NF-kappa B, is persistently activated in neurons that are destined to die. There are several potential routes through which NF-kappa B can act to induce neuronal death, including production of death proteins and an aborted attempt to reenter the cell cycle. NF-kappa B is only transiently activated in neurons that survive. Persistent NF-kappa B activation can be blocked by antioxidants, which suggests that the neuroprotective effect of antioxidants may be due to inhibiting activation of NF-kappa B.
Neuroscience Research, The Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, IN 46285, USA. clemens_james_a@lilly.com
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism* / Q000517:prevention & control; D005786:Gene Expression Regulation; D006801:Humans; D008959:Models, Neurological; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015533:Transcriptional Activation
D000975:Antioxidants; D016328:NF-kappa B; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species