Smith M A, Kutty R K, Richey P L, Yan S D, Stern D, Chader G J, Wiggert B, Petersen R B, Perry G
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106.
Am J Pathol. 1994 Jul;145(1):42-7.
Heme oxygenase-1 is an important enzyme that degrades heme, a pro-oxidant, leading to the formation of antioxidant molecules. In this study we demonstrate by immunocytochemistry close association of heme oxygenase-1 with Alzheimer neurofibrillary pathology and with the neurofibrillary tangles found in progressive supranuclear palsy and subacute sclerosing panencephalitis. In Alzheimer's disease, using two different rabbit antisera against heme oxygenase-1 protein, we localized, using immunocytochemical methods, heme oxygenase-1 to neurofibrillary tangles, senile plaque neurites, granulovacuolar degeneration, and neuropil threads. Only light background staining was seen in young controls and sporadic lesion-related immunoreactivity in age-matched controls. The increase in heme oxygenase-1 protein in association with the neurofibrillary pathology of Alzheimer's disease and other diseases characterized by neurofibrillary tangles supports the notion that the generation of free radicals and oxidative stress plays a role in the pathogenesis of neurofibrillary pathology.
血红素加氧酶-1是一种重要的酶,可降解作为促氧化剂的血红素,从而导致抗氧化分子的形成。在本研究中,我们通过免疫细胞化学方法证明,血红素加氧酶-1与阿尔茨海默病神经纤维病理以及进行性核上性麻痹和亚急性硬化性全脑炎中发现的神经纤维缠结密切相关。在阿尔茨海默病中,我们使用两种针对血红素加氧酶-1蛋白的不同兔抗血清,通过免疫细胞化学方法将血红素加氧酶-1定位到神经纤维缠结、老年斑神经突、颗粒空泡变性和神经毡丝中。在年轻对照中仅可见轻度背景染色,在年龄匹配的对照中可见散发性病变相关免疫反应性。与阿尔茨海默病和其他以神经纤维缠结为特征的疾病的神经纤维病理相关的血红素加氧酶-1蛋白增加支持了自由基生成和氧化应激在神经纤维病理发病机制中起作用的观点。