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雄激素受体多聚谷氨酰胺序列扩展对NG108-15细胞增殖的影响。

Effects of androgen receptor polyglutamine tract expansion on proliferation of NG108-15 cells.

作者信息

Nakajima H, Kimura F, Nakagawa T, Ikemoto T, Furutama D, Shinoda K, Kato S, Shimizu A, Ohsawa N

机构信息

First Department of Internal Medicine, Osaka Medical College, Takatsuki City, Japan.

出版信息

Neurosci Lett. 1997 Jan 31;222(2):83-6. doi: 10.1016/s0304-3940(97)13348-1.

DOI:10.1016/s0304-3940(97)13348-1
PMID:9111734
Abstract

Expansion of the polyglutamine tracts in the androgen receptor (AR) has been recognized as a cause of X-linked spinal and bulbar muscular atrophy (SBMA). In the present study, NG108-15 cells were stably transfected with expression vectors coding for either the wild type (WT) AR gene (CAG repeat number = 22) or a mutated (MT) AR gene (CAG repeat number = 52). Cells proliferation and cell cycle parameters were evaluated for NG108-15-WT and NG108-15-MT cells in the presence or absence of androgen. NG108-15-WT cells demonstrated an androgen-dependent increase in cell number, while NG108-15-MT cells did not. Our results demonstrate that expansion of polyglutamine tracts in the AR may affect the proliferation and differentiation of nerve cells.

摘要

雄激素受体(AR)中聚谷氨酰胺序列的扩增已被确认为X连锁脊髓和延髓性肌萎缩症(SBMA)的病因。在本研究中,用编码野生型(WT)AR基因(CAG重复次数 = 22)或突变型(MT)AR基因(CAG重复次数 = 52)的表达载体稳定转染NG108-15细胞。在有或没有雄激素存在的情况下,评估NG108-15-WT和NG108-15-MT细胞的细胞增殖和细胞周期参数。NG108-15-WT细胞显示出雄激素依赖性的细胞数量增加,而NG108-15-MT细胞则没有。我们的结果表明,AR中聚谷氨酰胺序列的扩增可能会影响神经细胞的增殖和分化。

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Effects of androgen receptor polyglutamine tract expansion on proliferation of NG108-15 cells.雄激素受体多聚谷氨酰胺序列扩展对NG108-15细胞增殖的影响。
Neurosci Lett. 1997 Jan 31;222(2):83-6. doi: 10.1016/s0304-3940(97)13348-1.
2
Transcriptional activation by the androgen receptor in X-linked spinal and bulbar muscular atrophy.
J Neurol Sci. 1996 Oct;142(1-2):12-6. doi: 10.1016/0022-510x(96)00142-6.
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Truncated forms of the androgen receptor are associated with polyglutamine expansion in X-linked spinal and bulbar muscular atrophy.雄激素受体的截短形式与X连锁脊髓和延髓性肌萎缩中的多聚谷氨酰胺扩增相关。
Hum Mol Genet. 1998 Jan;7(1):121-7. doi: 10.1093/hmg/7.1.121.
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Androgen induced cell death in SHSY5Y neuroblastoma cells expressing wild-type and spinal bulbar muscular atrophy mutant androgen receptors.雄激素诱导表达野生型和脊髓延髓肌肉萎缩突变型雄激素受体的SHSY5Y神经母细胞瘤细胞死亡。
Biochim Biophys Acta. 2001 Apr 30;1536(1):13-20. doi: 10.1016/s0925-4439(01)00029-1.
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[Triplet repeat disease, with particular emphasis of spinal and bulbar muscular atrophy (SBMA)].[三联体重复疾病,尤其侧重于脊髓延髓肌萎缩症(SBMA)]
Rinsho Shinkeigaku. 2000 Dec;40(12):1193-5.
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Protective effects of estrogens on polyglutamine-expanded androgen receptor aggregation in mice.雌激素对小鼠中多聚谷氨酰胺扩展雄激素受体聚集的保护作用。
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Motoneuronal cell death is not correlated with aggregate formation of androgen receptors containing an elongated polyglutamine tract.运动神经元细胞死亡与含有延长的多聚谷氨酰胺序列的雄激素受体的聚集形成无关。
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Androgen receptors containing expanded polyglutamine tracts exhibit progressive toxicity when stably expressed in the neuroblastoma cell line, SH-SY 5Y.
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Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy.在X连锁性脊髓延髓肌肉萎缩症小鼠模型中,内源性雄激素受体蛋白的缺失加速了运动神经元变性,并加剧了雄激素不敏感性。
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Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility.雄激素受体中的长聚谷氨酰胺序列与转录激活减少、精子生成受损及男性不育相关。
J Clin Endocrinol Metab. 1997 Nov;82(11):3777-82. doi: 10.1210/jcem.82.11.4385.

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