Hara Tsuyoshi, Hamada Jun-ichiro, Yano Shigetoshi, Morioka Motohiro, Kai Yutaka, Ushio Yukitaka
Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan.
J Neurochem. 2003 Aug;86(4):805-14. doi: 10.1046/j.1471-4159.2003.01847.x.
Ischemic tolerance is well known as a neuroprotective effect of pre-conditioning ischemia against delayed neuronal death, however, the mechanism or mechanisms underlying this effect are not fully understood. We investigated the relationship between CREB and ischemic tolerance in gerbil hippocampal CA1 neurons using CRE decoy oligonucleotide. Sublethal ischemia led to an increase in the level of CREB phosphorylation in CA1 regions while lethal ischemia did not. Experiments with NG108-15 cells showed that adding CRE decoy oligonucleotide to culture media significantly inhibited the cell growth rate. The administration of CRE decoy oligonucleotide into gerbil cerebral ventricle decreased CREB-DNA binding activity to 38% of the control. Pre-treatment with CRE decoy oligonucleotide 24 h before the induction of ischemic tolerance decreased CA1 neuronal cell survival to 21% of the control. The present findings suggest that a CREB-mediated transcription system is necessary for the induction of ischemic tolerance.
缺血耐受作为预处理缺血对延迟性神经元死亡的神经保护作用已广为人知，然而，这种作用的潜在机制尚未完全明确。我们使用CRE诱饵寡核苷酸研究了沙鼠海马CA1神经元中CREB与缺血耐受之间的关系。亚致死性缺血导致CA1区CREB磷酸化水平升高，而致死性缺血则未导致这种情况。对NG108-15细胞进行的实验表明，向培养基中添加CRE诱饵寡核苷酸可显著抑制细胞生长速率。将CRE诱饵寡核苷酸注入沙鼠脑室后，CREB-DNA结合活性降至对照组的38%。在诱导缺血耐受前24小时用CRE诱饵寡核苷酸预处理，可使CA1神经元细胞存活率降至对照组的21%。目前的研究结果表明，CREB介导的转录系统对于诱导缺血耐受是必需的。
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