Induction of Pi Form of Glutathione S-Transferase by Carnosic Acid Is Mediated through PI3K/Akt/NF-魏B Pathway and Protects against Neurotoxicity

详细信息    查看全文

• 作者：Chia-Yuan Lin ; Jing-Hsien Chen ; Ru-Huei Fu ; Chia-Wen Tsai
• 刊名：Chemical Research in Toxicology
• 出版年：2014
• 出版时间：November 17, 2014
• 年：2014
• 卷：27
• 期：11
• 页码：1958-1966
• 全文大小：372K
• ISSN：1520-5010

文摘

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 渭M CA followed by treatment with 100 渭M 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 I魏B kinase (IKK) and I魏B伪, p65 nuclear translocation, and nuclear factor-kappa B (NF-魏B)-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-魏B pathway. Therefore, CA may be a promising candidate for use in the prevention of Parkinson鈥檚 disease.