베타아밀로이드로 유도된 신경소교세포 사멸에 대한 루테올린의 보호효과 연구

Abstract

Objectives : The purpose of this study is to investigate neuroprotective effects and molecular mechanisms of luteolin against β -amyloid (Aβ 25-35)-induced oxidative cell death in BV-2 cells. Methods : The protective effects of luteolin against Aβ25-35-induced cytotoxicity and apoptotic cell death were determined by MTT dye reduction assay and TUNEL staining, respectively. The apoptotic cell death was further analyzed by measuring mitochondrial transmembrane potential and expression of pro- and/or anti-apoptotic proteins. To elucidate the molecular mechanisms underlying the protective effects of luteolin, intracellular accumulation of reactive oxygen species, oxidative damages, and expression of antioxidant enzymes were examined. Results : Luteolin pretreatment effectively attenuated Aβ 25-35-induced apoptotic cell death indices such as DNA fragmentation, dissipation of mitochondrial transmembrane potential, increased Bax/Bcl-2 ratio, and activation of c-Jun N-terminal kinase and caspase-3 in BV-2 cells. Furthermore, Aβ 25-35-induced intracellular formation of reactive oxygen species and subsequent oxidative damages such as lipid peroxidation and depletion of endogenous antioxidant glutathione were suppressed by luteolin treatment. The neuroprotective effects of luteolin might be mediated by up-regulation of cellular antioxidant defense system via up-regulation of γ -glutamylcysteine ligase, a rate-limiting enzyme in the glutathione biosynthesis and superoxide dismutase, an enzyme involved in dismutation of superoxide anion into oxygen and hydrogen peroxide. Conclusions : These findings suggest that luteolin has a potential to protect against Aβ 25-35-induced neuronal cell death and damages thereby exhibiting therapeutic utilization for the prevention and/or treatment of Alzheimer’s disease.