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甲磺酸麦角隐亭治疗后成人及老年大脑中带3蛋白的翻译后变化,与阿尔茨海默病中观察到的变化比较

Posttranslational changes in band 3 in adult and aging brain following treatment with ergoloid mesylates, comparison to changes observed in Alzheimer's disease.

作者信息

Cover C C, Poulin J E, Gustafson M R, Wyant T, Gamble D N, Kay M M

机构信息

International Foundation for Biomedical Aging Research, Temple, TX 76503, USA.

出版信息

Life Sci. 1996;58(8):655-64. doi: 10.1016/s0024-3205(96)80004-x.

Abstract

Band 3, the most heavily used anion transport system in vertebrates, ages as cells and tissues age. Posttranslational changes in band 3 in adult and aging brain were investigated following treatment with ergoloid mesylates and compared to changes observed in Alzheimer's disease (AD). The study was conducted in a double blind fashion and was decoded only after the study was completed. The following posttranslational changes in brain band 3 occur with age: increased breakdown of band 3; decreased phosphorylation; and decreased anion transport. Autoantibodies to senescent cell antigen (SCA) synthetic peptides residue 538-554 and 812-827 increase with age, but antibodies to the former peptide are significantly reduced in ergoloid mesylate treated old mice. This is a critical transport region of band 3. Results showed the aged/altered band 3 increased in Alzheimer's disease (AD) as determined by quantitative antibody binding. Ergoloid mesylates altered the age-related posttranslational changes as follows: the observed age-related decrease in brain band 3 was partially reversed and anion transport was increased. This is consistent with the data indicating decreased autoantibodies to a critical anion transport segment of band 3. Aging appears to result in damage to a critical transport region of the anion transporter which is reflected by decreased anion transport, increased breakdown, alteration of the molecule itself, and an increase in autoantibodies to the region. Ergoloid mesylates seem to protect against this damage.

摘要

带3是脊椎动物中使用最频繁的阴离子转运系统,会随着细胞和组织的衰老而老化。在用甲磺酸麦角隐亭治疗后,研究了成年和衰老大脑中带3的翻译后变化,并与阿尔茨海默病(AD)中观察到的变化进行了比较。该研究以双盲方式进行,仅在研究完成后才进行解码。大脑带3的以下翻译后变化会随着年龄的增长而出现:带3的分解增加;磷酸化减少;阴离子转运减少。针对衰老细胞抗原(SCA)合成肽残基538 - 554和812 - 827的自身抗体随年龄增加,但在甲磺酸麦角隐亭治疗的老年小鼠中,针对前一种肽的抗体显著减少。这是带3的一个关键转运区域。结果表明,通过定量抗体结合测定,在阿尔茨海默病(AD)中,老化/改变的带3增加。甲磺酸麦角隐亭改变了与年龄相关的翻译后变化,如下所示:观察到的大脑带3与年龄相关的减少部分得到逆转,阴离子转运增加。这与表明针对带3关键阴离子转运片段的自身抗体减少的数据一致。衰老似乎会导致阴离子转运体的关键转运区域受损,这表现为阴离子转运减少、分解增加、分子本身改变以及该区域自身抗体增加。甲磺酸麦角隐亭似乎可以防止这种损伤。

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