Inhibitory Effect of Flavonoid Luteolin on 6-Hydroxydopamine
Cytotoxicity via Suppression of Apoptosis-Related Protein Activation

J Korean Neurol Assoc > Volume 30(4); 2012 > Article

Journal of the Korean Neurological Association 2012;30(4): 284-292.

플라보노이드 luteolin이 세포자멸사 관련 단백질 활성 억제를 통해 6-hydroxydopamine 세포독성에 미치는 억제효과

이선화, 강진호 한정호 김두응 이정수 a

중앙보훈병원 신경과, 중앙대학교 의과대학 약리학교실 a

Inhibitory Effect of Flavonoid Luteolin on 6-Hydroxydopamine Cytotoxicity via Suppression of Apoptosis-Related Protein Activation

Seon-Wha Lee

Department of Neurology, Veterans Health Service Medical Center, Seoul, Korea Department of Pharmacology a , Chung-Ang University College of Medicine, Seoul, Korea

Abstract

Background: Flavonoid luteolin has been shown to exhibit cell protective effect. However, it is still uncertain whether the effect of luteolin on cellular toxicity of the parkinsonian toxin 6-hydroxydopamine is mediated by apoptosis-related protein activation.
Methods: In differentiated PC12 cells exposed to 6-hydroxydopamine in combination with luteolin, we observed the apoptosis-related protein activation, nuclear damage, formation of reactive oxygen species and cell death.
Results: 6-Hydroxydopamine caused apoptosis by inducing a decrease in Bid, Bcl-2, Bcl-xL and survivin levels, increase in Bax levels, cytochrome c release and activation of caspases. Treatment with luteolin reduced changes in the apoptosis-related protein levels, formation of reactive oxygen species, nuclear damage and cell death.
Conclusions: Luteolin may reduce the 6-hydroxydopamine-induced apoptosis in differentiated PC12 cells by suppressing the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway, leading to caspase activation. The preventive effect of luteolin may be associated with its inhibitory effect on the production of reactive oxygen species. Luteolin may attenuate the oxidative stress and mitochondrial dysfunction-induced neuronal cell death take place in Parkinson’s disease. Key Words: 6-Hydroxydopamine, Apoptosis-related proteins, Flavonoid luteolin, PC12 cells, Protective effect, Reactive oxygen species