Brain protein and α‐ketoglutarate dehydrogenase complex activity in alzheimer‐s disease
Brain protein and α‐ketoglutarate dehydrogenase complex activity in alzheimer‐s disease
复制标题
阿尔茨海默病中的脑蛋白和α-酮戊二酸脱氢酶复合物活性
作者：
F. Mastrogiacomo;J. Lindsay;L. Bettendorff;J. Rice;S. Kish
为了确定阿尔茨海默病 (AD) 中大脑 α-酮戊二酸脱氢酶复合物活性的降低是否与其三个组成酶亚基之一的异常相关，我们测量了 29 名 AD 患者死后大脑中 α-酮戊二酸脱氢酶 (El)、二氢硫辛酰胺琥珀酰转移酶 (E2) 和二氢硫辛酰胺脱氢酶 (E3) 的蛋白质水平（平均年龄为 73 岁）岁；发病年龄范围，50-78 岁）和 29 名对照受试者。在AD组中，颞叶皮层中所有三个亚基的蛋白质水平均显着降低23%至41%，而在顶叶皮层（E1：-28%、E3：-32%）和海马体（E3：-33%）中，显着变化仅限于E1和E3。 α-酮戊二酸脱氢酶复合物活性更显着降低（降低了 46-68%），并且与蛋白质水平无关，表明酶活性降低不能主要用 α-酮戊二酸脱氢酶复合物蛋白的损失来解释。我们没有在任何患者的大脑中发现两种 E2 免疫反应形式，正如在极早发型 14 号染色体连锁 AD 患者的成纤维细胞中所报道的那样。我们得出的结论是，50 年后发病的 AD 患者的脑蛋白和 α-酮戊二酸脱氢酶复合物的活性水平降低，并表明这些变化（在其他人类大脑疾病中也观察到）可能代表不同神经退行性过程的非特异性后果。然而，克雷布斯循环限速酶水平的降低可能会导致 AD 的大脑神经退行性机制。
To determine whether the reduction in brain α‐ketoglutarate dehydrogenase complex activity in Alzheimer's disease (AD) is associated with an abnormality in one of its three constituent enzyme subunits, we measured protein levels of α‐ketoglutarate dehydrogenase (El), dihydrolipoamide succinyltransferase (E2), and dihydrolipoamide dehydrogenase (E3), in postmortem brain of 29 patients with AD (mean age, 73 years; age range of onset, 50‐78 years) and 29 control subjects. In the AD group protein levels of all three subunits were significantly reduced by 23 to 41% in the temporal cortex, whereas in the parietal cortex (El: −28% E3: −32%) and hippocampus (E3: −33%) significant changes were limited to El and E3. α‐Ketoglutarate dehydrogenase complex activities were more markedly reduced (by 46‐68%) and did not correlate with protein levels, suggesting that decreased enzyme activity cannot be primarily explained by loss of α‐ketoglutarate dehydrogenase complex protein. We did not find two E2 immunoreactive forms in the brain of any patient, as has been reported in fibroblasts of patients with very‐early‐onset chromosome 14‐linked AD. We conclude that brain protein and activity levels of α‐ketoglutarate dehydrogenase complex are reduced in patients with AD who have onset after 50 years and suggest that these changes, which are also observed in other human brain disorders, may represent a nonspecific consequence of different neurodegenerative processes. Nevertheless, reduced levels of this ratelimiting enzyme of the Krebs cycle could contribute to the brain neurodegenerative mechanisms of AD.
DOI：
10.1016/s0021-9258(17)36875-8
发表时间：
1994-05
期刊：
The Journal of biological chemistry
影响因子：
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作者：
D. Gabuzda;J. Busciglio;Lanren Chen;P. Matsudaira;B. Yankner
通讯作者：
D. Gabuzda;J. Busciglio;Lanren Chen;P. Matsudaira;B. Yankner
影响因子：
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作者：
SHEU, KFR;CLARKE, DD;DECICCO, J
通讯作者：
DECICCO, J
影响因子：
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作者：
GIBSON, GE;SHEU, KFR;PERRINO, P
通讯作者：
PERRINO, P