Department of Microbiology & Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ 07101-1709, USA.
J Alzheimers Dis. 2010;19(4):1177-83. doi: 10.3233/JAD-2010-1311.
Elevated plasma homocysteine (Hcy) is a risk factor for Alzheimer's disease (AD). Bleomycin hydrolase (BLH), a thiol-dependent enzyme that has Hcy-thiolactonase (HTase) and aminopeptidease (APase) activities, has also been implicated in Alzheimer's disease (AD). In order to examine its role in AD, BLH activities were measured in postmortem brain tissue from twelve AD patients and twelve control patients who died from non-neurological causes. We found that HTase and APase activities in human brain extracts were strongly correlated and sensitive to the thiol reagent iodoacetamide, indicating that they are associated with BLH. Both activities were significantly decreased in brain tissue extracts from AD patients relative to controls (7.6 +/- 4.2 vs. 13.5 +/- 5.5 units, p= 0.003 for HTase, and 3.82 +/- 1.27 vs. 5.33 +/- 1.68 units, p=0.010 for APase). HTase and APase activities were positively correlated with N-linked protein Hcy, but not with tHcy, in AD and control brains. Levels of brain total Hcy and N-linked protein Hcy did not differ between AD cases and controls. These results suggest that diminished functional BLH activity could contribute to the pathology of AD.
血浆同型半胱氨酸（Hcy）升高是阿尔茨海默病（AD）的危险因素。 丝氨酸依赖酶— 丝氨酸内肽酶（BLH），具有 Hcy-硫内酯酶（HTase）和氨肽酶（APase）活性，也与阿尔茨海默病（AD）有关。为了研究其在 AD 中的作用，我们测量了 12 名 AD 患者和 12 名因非神经原因死亡的对照患者死后脑组织中的 BLH 活性。我们发现人脑提取物中的 HTase 和 APase 活性具有强相关性，并对硫醇试剂碘乙酰胺敏感，表明它们与 BLH 相关。与对照组相比，AD 患者脑组织提取物中的 HTase 和 APase 活性显著降低（HTase 为 7.6±4.2 对 13.5±5.5 单位，p=0.003；APase 为 3.82±1.27 对 5.33±1.68 单位，p=0.010）。HTase 和 APase 活性与 AD 和对照脑内的 N-连接蛋白 Hcy 呈正相关，但与 tHcy 无关。AD 病例和对照组之间的脑总 Hcy 和 N-连接蛋白 Hcy 水平没有差异。这些结果表明，功能下降的 BLH 活性可能导致 AD 的病理。
