http://scholars.ntou.edu.tw/handle/123456789/23808
標題: | Induction of Pi form of glutathione S-transferase by carnosic acid is mediated through PI3K/Akt/NF-κB pathway and protects against neurotoxicity | 作者: | Lin, Chia-Yuan Chen, Jing-Hsien Fu, Ru-Huei Tsai, Chia-Wen |
關鍵字: | NF-KAPPA-B;DOPAMINE-INDUCED APOPTOSIS;PARKINSONS-DISEASE;CELL-DEATH;C-JUN;OXIDATIVE STRESS;HEME OXYGENASE-1;TERMINAL KINASE;EXPRESSION;ACTIVATION | 公開日期: | 17-十一月-2014 | 出版社: | AMER CHEMICAL | 卷: | 27 | 期: | 11 | 起(迄)頁: | 1958-1966 | 來源出版物: | Chemical research in toxicology | 摘要: | Carnosic acid (CA), a diterpene found in the rosemary (Rosmarinus officinalis), has been reported to have a neuroprotective effect. Glutathione S-transferase (GST) P (GSTP) is a phase II detoxifying enzyme that provides a neuroprotective effect. The aim of this study was to explore whether the neuroprotective effect of CA is via an upregulation of GSTP expression and the possible signaling pathways involved. SH-SY5Y cells were pretreated with 1 μM CA followed by treatment with 100 μM 6-hydroxydopamine (6-OHDA). Both immunoblotting and enzyme activity results show that CA also induced protein expression and enzyme activity of GSTP. Moreover, CA significantly increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt, the nuclear translocation of p65, but not mitogen-activated protein kinases (p < 0.05). Pretreatment with LY294002 (a PI3K/Akt inhibitor) suppressed the CA-induced phosphorylation of IκB kinase (IKK) and IκBα, p65 nuclear translocation, and nuclear factor-kappa B (NF-κB)-DNA binding activity as well as GSTP protein expression. Furthermore, CA attenuated 6-OHDA-induced caspase 3 activation, and cell death was reversed by GSTP siRNA or LY294002 treatment. Additionally, male Wistar rats with lesions induced by 6-OHDA treatment in the right striatum responded to treatment with CA, which significantly reversed the reduction in GSTP protein expression that resulted from lesioning. We suggest that CA prevents 6-OHDA-induced apoptosis through an increase in GSTP expression via activation of the PI3K/Akt/NF-κB pathway. Therefore, CA may be a promising candidate for use in the prevention of Parkinson's disease. |
URI: | http://scholars.ntou.edu.tw/handle/123456789/23808 | ISSN: | 0893-228X 1520-5010 |
DOI: | 10.1021/tx5003063 |
顯示於: | 食品科學系 |
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