Marmillot P, Rao M N, Liu Q H, Lakshman M R
Department of Veterans Affairs Medical Center, Department of Medicine, The George Washington University, Washington, DC 20422, USA.
Alcohol Clin Exp Res. 1999 Feb;23(2):376-80.
In view of the chronic alcohol-mediated pathological changes in various sialic acid-deficient glycoconjugates and the potential importance of sialidase in the generation of these glycoconjugates in the blood compartment and in the brain, we have investigated the effects of chronic ethanol feeding for 8 weeks on ganglioside sialidase activities in rat blood and brain. Ganglioside sialidase activity in erythrocytes (whether expressed as units/mg of protein or units/ml of blood) was 1.37- to 1.40-fold higher (p < 0.01) in the ethanol-fed group than in the control group. On the other hand, the same ethanol treatment increased sialidase activity in the leukocyte soluble fraction by 2.50- to 2.60-fold (p < 0.01) and by 1.61- to 1.63-fold (p < 0.01) in the leukocyte particulate fraction, compared with the control group. More importantly, most of the blood compartment sialidase activity was localized in the leukocytes particulate fraction (80 to 86% of total blood activity). Similarly, chronic ethanol treatment increased brain synaptosomal sialidase activity (whether expressed as units/gram of brain or units/mg of protein) 2.16- to 2.43-fold (p < 0.01). In contrast, brain lysosomal sialidase was not significantly altered by ethanol treatment, even though the major proportion of the brain sialidase activity was localized in the lysosomes. The proportion of synaptosomal sialidase activity as the percentage of total brain sialidase activity increased markedly from 13% in the control group to 24% in the ethanol group. Thus, chronic ethanol-mediated increases in sialidase activity in the leukocytes and brain synaptosomes could account for alterations in the ganglioside status of the animal and consequent adverse effects of chronic ethanol on behavioral and pathological changes.
鉴于慢性酒精介导的各种唾液酸缺乏的糖缀合物的病理变化，以及唾液酸酶在血液和大脑中这些糖缀合物生成中的潜在重要性，我们研究了8周慢性乙醇喂养对大鼠血液和大脑中神经节苷脂唾液酸酶活性的影响。乙醇喂养组红细胞中的神经节苷脂唾液酸酶活性（无论以单位/毫克蛋白质还是单位/毫升血液表示）比对照组高1.37至1.40倍（p<0.01）。另一方面，与对照组相比，相同的乙醇处理使白细胞可溶性部分的唾液酸酶活性增加了2.50至2.60倍（p<0.01），在白细胞颗粒部分增加了1.61至1.63倍（p<0.01）。更重要的是，大部分血液中的唾液酸酶活性位于白细胞颗粒部分（占血液总活性的80%至86%）。同样，慢性乙醇处理使脑突触体唾液酸酶活性（无论以单位/克脑或单位/毫克蛋白质表示）增加了2.16至2.43倍（p<0.01）。相比之下，尽管大脑中大部分唾液酸酶活性位于溶酶体中，但乙醇处理并未显著改变脑溶酶体唾液酸酶活性。突触体唾液酸酶活性占大脑总唾液酸酶活性的百分比从对照组的13%显著增加到乙醇组的24%。因此，慢性乙醇介导的白细胞和脑突触体中唾液酸酶活性的增加可能解释了动物神经节苷脂状态的改变以及慢性乙醇对行为和病理变化的后续不良影响。
