Department of Human Morphology and Biomedical Sciences Città Studi, University of Milan, Via Mangiagalli 31 Milano, Italy.
Toxicol In Vitro. 2010 Apr;24(3):815-21. doi: 10.1016/j.tiv.2009.12.012. Epub 2009 Dec 13.
Down's syndrome (DS) is characterized by several pathological aspects leading to an increased susceptibility to cardiovascular diseases, infections, leukemia, endocrine alterations. DS patients display some of the physiopathological characteristics of aging, observed also in Alzheimer disease (AD), such as abnormalities in lipids metabolism, diabetes, high cholesterol fraction, senile plaques and neurofibrillary tangles. For this reason DS is considered a precocious and accelerated model of senescence, in which increased apoptosis is the main cornerstone. In order to better understand the apoptotic process in pathological cellular aspects of DS, the aim of this study was to investigate the apoptotic response of DS fibroblasts to OA, a toxin that induces malformations and inhibits growth in different cell lines. We focused specifically on the mitochondrial response by investigating changes in mitochondrial membrane potential (evaluate by flow cytometry and fluorescence microscopy using JC-1 probe) and alterations of mitochondrial outer membrane (evaluated by flow cytometry using annexin V/propidium iodide). Results indicates that DS Fibroblasts have a baseline of apoptosis higher than normal fibroblasts and are more susceptible to the pro-apoptotic effect of OA. Understanding the mechanism of apoptosis in DS fibroblasts could provide new insight in the pathogenic mechanism of this pathology and suggest potential therapeutical targets to the clinical treatment at complex diseases associated to this pathology.
唐氏综合征（DS）的特征是多个病理方面，导致其易患心血管疾病、感染、白血病和内分泌改变。DS 患者表现出一些与衰老相关的病理生理特征，这些特征也在阿尔茨海默病（AD）中观察到，如脂代谢异常、糖尿病、高胆固醇、老年斑和神经原纤维缠结。因此，DS 被认为是衰老的一种早熟和加速模型，其中细胞凋亡增加是主要基石。为了更好地理解 DS 病理细胞中细胞凋亡的过程，本研究旨在研究 OA 对 DS 成纤维细胞凋亡的反应，OA 是一种诱导畸形和抑制不同细胞系生长的毒素。我们特别关注线粒体反应，通过流式细胞术和使用 JC-1 探针的荧光显微镜研究线粒体膜电位的变化（评估），并通过流式细胞术使用 Annexin V/碘化丙啶评估线粒体外膜的改变（评估）。结果表明，DS 成纤维细胞的凋亡基线高于正常成纤维细胞，并且对 OA 的促凋亡作用更敏感。了解 DS 成纤维细胞凋亡的机制可以为该病理学的发病机制提供新的见解，并为与该病理学相关的复杂疾病的临床治疗提供潜在的治疗靶点。
