Mitochondrial function in fibroblasts with aging in culture and/or Alzheimer's disease

Mitochondrial function in fibroblasts with aging in culture and/or Alzheimer's disease
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DOI:
10.1016/j.neurobiolaging.2004.07.012
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发表时间:
2005-06-01
影响因子:
4.2
通讯作者:
Gibson, GE
Gibson, GE
中科院分区:
医学2区
文献类型:
--
作者:
Huang, HM;Fowler, C;Gibson, GE

文献摘要

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线粒体膜电位(MMP)反映了细胞内线粒体的功能状态。我们最近发表的方法提供了一个定量估计MMP的群体中的类胶质细胞颗粒(MLP)在37摄氏度的活细胞内,使用传统的荧光显微镜,三维去卷积和穷举光子重新分配(EPR)的组合。尽管该方法不提供MMP的绝对测量,但这些相对MMP允许直接比较培养物中不同年龄的细胞中的各种线粒体和来自多个患者的不同细胞系中的各种线粒体。成纤维细胞系从四个阿尔茨海默病(AD)患者轴承早老素-1(PS-1)突变和四个适当的控制进行了评估,在不同的年龄在文化。结果显示,在每个细胞或每个细胞系内,所有MLP的相对MMP、细胞大小和相对MMP的总和存在很大差异。然而,结合各组细胞系的相对MMP值,发现培养物中随年龄分布的变化。成纤维细胞的相对MMP随年龄的增长而减小,而细胞大小和每个细胞内相对MMP的总和则随年龄的增长而增加。在任何年龄的培养物中,对照组和携带PS-1突变的AD患者之间的值没有差异。这种新的,敏感的和定量的估计相对MMP表明,在非应激条件下,相对MMP的变化与文化中的老化,但相对MMP之间没有显着差异控制和AD主题。(c)2004年爱思唯尔公司All rights reserved.
Mitochondrial membrane potentials (MMP) reflect the functional state of the mitochondria within cells. Our recently published method provides a quantitative estimate of the MMP of populations of mitochondrial-like particles (MLP) within living cells at 37 degrees C using the combination of conventional fluorescence microscopy, 3D-deconvolution and exhaustive photon reassignment (EPR). Although the method does not provide an absolute measure of MMP, these relative MMP allow direct comparison between various mitochondria in cells at various ages in culture and in different cell lines from multiple patients. Fibroblasts lines from four Alzheimer's disease (AD) patients bearing the presenilin-1 (PS-1) mutation and four appropriate controls were evaluated at different ages in culture. The results showed a large variation in the relative MMP, cell size and sum of relative MMP of all MLP within each cell or within each cell line. Nevertheless, combining the values of relative MMP for the cell lines in each group revealed changes in distribution with age in culture. The relative MMP decreased while the cell sizes and sum of relative MMP within each cell increased with age in fibroblasts. Values did not differ between controls and the AD patients bearing PS-1 mutation at any age in cultures. This new, sensitive and quantitative estimate of relative MMP indicates that under non-stressed conditions relative MMP change with aging in culture, but relative MMP do not differ between controls and AD subjects. (c) 2004 Elsevier Inc. All rights reserved.