Anti-apoptotic action of polyphenols derived from red wine and green tea against beta-amyloid in hippocampal cells
Author: Stéphane Bastianetto and Slavica Krantic and Rémi Quirion
Background: It has been suggested that accumulation of amyloid-beta (Aß) peptides into senile plaques plays a pivotal role in neuronal cell death occuring in Alzheimer's disease (AD). Aß produces two major types of programmed cell death (PCD) in vitro which requires the activation of effectors of caspase-dependent and -independent cell death pathways, namely caspase-3 and apoptosis inducing factor (AIF). Published data comparing the expression of AIF in post-mortem brains from AD patients and neurologically normal subjects in the course of aging suggest the relevance of AIF in the pathogenesis of AD Reix et al, Neurobiol Aging 28:351, 2007; Yu et al., Am. J. Path., in press). Recent epidemiological studies have reported that elderly people have a lower risk (up to 50%) to develop AD if they regularly eat fruits and vegetables and drink a moderate amount of tea and red wine. Numerous studies indicate that polyphenols derived from these foods and beverages account for the observed neuroprotective effects. In particular, polyphenols extracted from green tea (i.e. epigallocatechin gallate or EGCG) or red wine (i.e. resveratrol) blocked hippocampal cell death against Aß-induced toxicity (Bastianetto et al, Eur J Neurosci 23:55, 2006; Han et al, Br J Pharmacol 141:997, 2004). Our main objective is to determine whether concurrent inactivation of both main types of PCD may have additive therapeutic benefit in AD. Methods: Mixed hippocampal cell cultures were prepared from E19 fetuses obtained from Sprague-Dawley rats. They were grown in D-MEM high glucose containing 10% (v/v) fetal bovine serum. Experiments were performed in 6-day-old cultures. Results: The 24-hour exposure of cultured hippocampal cells to Aß1-42 (15 μM) alone or in combination with either resveratrol (20 μM) or EGCG (10 μM) reduced Aß1-42-mediated increased expression of the 57 kDa death-inducing form of AIF. Moreover, EGCG completely inhibited the activation of the key apoptotic executioner, caspase-3, and reduce the number of apoptotic cells, whereas resveratrol was less effective. Conclusions: Our findings show that these polyphenols do not share the same mechanism of action, suggesting that a combination of EGCG and resveratrol might provide additional neuroprotection against Aß-associated cell death.