Heme oxygenase-1 (HO-1) protein induction in rat brain following focal ischemia
Heme oxygenase-1 (HO-1) protein induction in rat brain following focal ischemia
复制标题
DOI：
10.1016/0169-328x(95)00315-j
复制
发表时间：
1996-04-01
期刊：
影响因子：
--
通讯作者：
Sharp, FR
中科院分区：
文献类型：
--
作者：
Nimura, T;Weinstein, PR;Sharp, FR
将血红素加氧酶-1（HO-1）蛋白（也称为HSP 32）的诱导与局灶性缺血后HSP 70热休克蛋白的诱导进行比较。成年Sprague-Dawley雄性大鼠（n = 14）使用缝线、大脑中动脉（MCA）闭塞模型进行30 min或2 h的局灶性脑缺血。对照组（n = 4）进行假手术。再灌注24小时后，处死受试者，并对他们的大脑进行HO-1和HSP 70热休克蛋白的免疫细胞化学染色。缺血30 min后第1天，纹状体内HO-1和HSP 70染色主要见于梗死区的内皮细胞和梗死区周围的胶质细胞。缺血30 min后，大脑皮层HO-1未被诱导，而大脑中动脉分布的皮层神经元中HSP 70被诱导。大脑中动脉缺血2 h后第1天，大脑中动脉分布区皮质神经元中HO-1和HSP 70均被诱导表达。然而，HO-1，诱导在整个同侧皮质，内部以及外部的MCA分布的胶质细胞。这表明HO-1和HSP 70基因的翻译和/或转录在梗死内注定死亡的神经元和神经胶质中被阻断，而这些应激基因的翻译在内皮细胞中继续。在皮层神经元中诱导HSP 70所需的缺血持续时间似乎小于在皮层胶质细胞中诱导HO-1所需的缺血持续时间。长时间的扩散性抑制和/或弥漫性半球缺血可通过HO-1启动子中AP-1位点的立即早期基因激活在整个同侧皮层的神经胶质中诱导HO-1。由于HO-1将促氧化剂血红素降解为抗氧化分子，因此HO-1的诱导可能会增强脑缺血损害的氧化防御机制。
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.