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帕金森病女性患者端粒长度和亚端粒状态的衰老相关改变。

Aging-associated alteration of telomere length and subtelomeric status in female patients with Parkinson's disease.

作者信息

Maeda Toyoki, Guan Jing Zhi, Koyanagi Masamichi, Higuchi Yoshihiro, Makino Naoki

机构信息

Department of Cardiovascular, Respiratory and Geriatric Medicine, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, Oita, Japan.

出版信息

J Neurogenet. 2012 Jun;26(2):245-51. doi: 10.3109/01677063.2011.651665. Epub 2012 Feb 27.

Abstract

A telomere is a repetitive DNA structure at chromosomal ends that stabilizes the chromosome structure and prevents harmful end-to-end recombinations. The telomere length of somatic cells becomes shorter with aging because of the "end replication problem." This telomere shortening is accelerated by pathophysiological conditions including daily mental stress. Living with Parkinson's disease (PD) causes physical and mental stress; therefore, the authors hypothesized that the telomere length of somatic cells was shortened excessively in patients with PD. In order to detect PD-associated somatic telomeric alterations, the telomere length and subtelomeric methylation status of peripheral leukocytes of PD patients were assessed by Southern blotting, using methylation-sensitive and -insensitive isoschizomers. The results demonstrated that the peripheral leukocytes of Japanese female patients with PD bore fewer long telomeres and a proportional increase of hypomethylated subtelomeres in short telomeres in comparison with the healthy controls. This study indicates that with the neurodegeneration associated with PD, telomeric and subtelomeric structural alterations occur. These structural telomere alterations most likely occur secondary to the acceleration of aging-associated telomeric changes and the accelerated loss of cells bearing short telomeres.

摘要

端粒是染色体末端的一种重复DNA结构,它能稳定染色体结构并防止有害的端对端重组。由于“末端复制问题”,体细胞的端粒长度会随着衰老而变短。包括日常精神压力在内的病理生理状况会加速这种端粒缩短。帕金森病(PD)患者会面临身心压力;因此,作者推测PD患者体细胞的端粒长度会过度缩短。为了检测与PD相关的体细胞端粒改变,使用甲基化敏感和不敏感的同裂酶,通过Southern印迹法评估了PD患者外周血白细胞的端粒长度和亚端粒甲基化状态。结果表明,与健康对照相比,日本女性PD患者的外周血白细胞长端粒较少,短端粒中亚甲基化亚端粒成比例增加。这项研究表明,随着与PD相关的神经退行性变,端粒和亚端粒结构会发生改变。这些端粒结构改变很可能继发于与衰老相关的端粒变化加速以及携带短端粒细胞的加速丢失。

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