신경교 세포에서 resveratrol이 amyloid-β에 의해 유도되는 Cdk inhibitor p21 및 Bax 발현의 감소 효과

Abstract

Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. Amyloid-β deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease. In this study, we have explored the effects of resveratrol on amyloid-β-peptide-mediated cytotoxicity in vitro and modulation of cell growth-regulatory gene products in astroglioma C6 cells to elucidate its possible mechanism for anti-cytotoxicity. Exposure of C6 cells to amyloid-β resulted in dose-dependent growth inhibition and morphological changes of C6 cells, which were recovered by pre-treatment with resveratrol. The anti-proliferative effect of amyloid-β was associated with the induction of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) expression assessed by RT-PCR and Western blot analysis in time-dependent manner in C6 cells. In addition, the pro-apoptotic Bax expression was also up-regulated in amyloid-β-treated C6 cells without alteration of anti-apoptotic Bcl-2 and Bcl-XL expression. However, pre-treatment of resveratrol significantly inhibited amyloid-β-induced p53, p21 and Bax levels, suggesting that the modulation of p53, p21 and Bax levels could be one of the possible pathways by which resveratrol functions as anti-cytotoxic agent. Our results demonstrate that resveratrol may enhance the protection against amyloid-β-induced cytotoxicity by promoting the survival of glial cells.