Okadaic acid induces apoptosis in Down syndrome fibroblasts

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. (C) 2009 Elsevier Ltd. All rights reserved.