Nimura T, Weinstein P R, Massa S M, Panter S, Sharp F R
Department of Neurosurgery, University of California, San Francisco, USA.
Brain Res Mol Brain Res. 1996 Apr;37(1-2):201-8. doi: 10.1016/0169-328x(95)00315-j.
The induction of the heme oxygenase-1 (HO-1) protein, also called HSP32, was compared to HSP70 heat shock protein induction following focal ischemia. Adult Sprague-Dawley male rats (n = 14) were subjected to either 30 min or 2 h of focal cerebral ischemia using the suture, middle-cerebral-artery (MCA) occlusion model. Controls (n = 4) had sham surgery. Following 24 h of reperfusion, subjects were killed and their brains stained immunocytochemically for HO-1 and the HSP70 heat shock proteins. One day following 30 min of ischemia, HO-1 and HSP70 staining in striatum occurred mainly in endothelial cells in infarcts and in glial cells surrounding the areas of infarction. Following the 30 min ischemia HO-1 was not induced in cortex whereas HSP70 was induced in cortical neurons in the MCA distribution. One day following 2 h of MCA ischemia, both HO-1 and HSP70 were induced in neurons in cortex in the MCA distribution. HO-1, however, was induced in glial cells throughout ipsilateral cortex, inside as well as outside the MCA distribution. This suggests that translation and/or transcription of the HO-1 and HSP70 genes are blocked in neurons and glia destined to die within infarcts, whereas translation of these stress genes continues in the endothelial cells. The duration of ischemia required to induce HSP70 in cortical neurons appears to be less than that required to induce HO-1 in cortical glia. Prolonged spreading depression and/or diffuse hemispheric ischemia may induce HO-1 in glia throughout the ipsilateral cortex via immediate early gene activation of the AP-1 site in the HO-1 promoter. Since HO-1 degrades heme, a pro-oxidant, to antioxidant molecules, the induction of HO-1 may augment oxidative defense mechanisms compromised by cerebral ischemia.
将血红素加氧酶-1（HO-1）蛋白（也称为HSP32）的诱导与局灶性缺血后HSP70热休克蛋白的诱导进行了比较。成年雄性Sprague-Dawley大鼠（n = 14）使用缝线大脑中动脉（MCA）闭塞模型进行30分钟或2小时的局灶性脑缺血。对照组（n = 4）进行假手术。再灌注24小时后，处死实验对象，其大脑进行HO-1和HSP70热休克蛋白的免疫细胞化学染色。缺血30分钟后一天，纹状体中的HO-1和HSP70染色主要发生在梗死灶的内皮细胞和梗死区域周围的神经胶质细胞中。30分钟缺血后，皮质中未诱导出HO-1，而在MCA分布区域的皮质神经元中诱导出了HSP70。MCA缺血2小时后一天，MCA分布区域皮质中的神经元同时诱导出了HO-1和HSP70。然而，HO-1在同侧整个皮质的神经胶质细胞中均有诱导，包括MCA分布区域内外。这表明HO-1和HSP70基因的翻译和/或转录在梗死灶内注定死亡的神经元和神经胶质细胞中被阻断，而这些应激基因的翻译在内皮细胞中继续。在皮质神经元中诱导HSP70所需的缺血持续时间似乎比在皮质神经胶质细胞中诱导HO-1所需的时间短。长时间的扩散性抑制和/或弥漫性半球缺血可能通过HO-1启动子中AP-1位点的立即早期基因激活，在同侧整个皮质的神经胶质细胞中诱导HO-1。由于HO-1将促氧化剂血红素降解为抗氧化分子，HO-1的诱导可能增强因脑缺血而受损的氧化防御机制。
