Kaempferol Derivatives Prevent Oxidative Stress–Induced Cell Death in a DJ-1–Dependent Manner

Journal of Pharmacological Sciences

Shizuma Ishikawa⁴  Yun-chul Kim³  Li Fan²  Hiroyoshi Ariga³  Xiao-Ping Pu¹  Sanae M.M. Iguchi-Ariga⁴  Wei Qu³ 

[1] Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science, Peking University Health Science Center, China;Department of Natural Medicines, School of Pharmaceutical Science, Peking University Health Science Center, China;Laboratory of Molecular Biolgy, Graduate School of Pharmaceutical Sciences, Hokkaido University, Japan;Laboratory of Environmental Molecular Bioscience, Graduate School of Agriculture, Hokkaido University, Japan

关键词: DJ-1;    traditional Chinese medicine;    cell death;    oxidative stress;    Parkinson’s disease;   

DOI  :  10.1254/jphs.09045FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(37)Cited-By(12)DJ-1, a causative gene product of a familial form of Parkinson’s disease (PD), PARK7, plays a role in anti-oxidative stress, and loss of its function is thought to result in the onset of PD. Superfluous oxidation of cysteine at amino acid 106 (C106) of DJ-1 renders DJ-1 inactive, and such oxidized DJ-1 was observed in patients with the sporadic form of PD. In this study, we examined the relationship between DJ-1 and compounds extracted from traditional Chinese medicines possessing anti-oxidant activity. Of the 12 compounds tested, 5 were found to specifically bind to the C106 region by using a quartz crystal microbalance. Although 4 compounds prevented rat PC12 and primary neuronal cells from undergoing H2O2-induced cell death, the protective activity of 2 compounds, kaempferol 3-O-β-rutinoside and 6-hydroxykaempferol 3,6-di-O-β-D-glucoside, was diminished in cells transfected with siRNA targeting DJ-1, indicating DJ-1–dependent reaction of these compounds. Furthermore, these compounds reduced the level of reactive oxygen species and restored tyrosine hydroxylase activity that had been induced and compromised, respectively, by treatment of cells with H2O2. The results suggest that these compounds are useful lead compounds for PD therapy.

【 授权许可】

Unknown