Effects of (-)-sesamin on dopamine biosynthesis and 6-hydroxydopamine-induced neurotoxicity in PC12 cells
(+)-Sesamin enhances dopamine biosynthesis and reduces L-DOPA-induced cytotoxicity in PC12 cells. (-)-Sesamin and (+)-sesamin are epimeric isomer lignans. Here this study investigated the effects of (-)-sesamin on dopamine biosynthesis and 6-hydroxydopamine (6-OHDA)-induced neurotoxicity using PC12 cells and 6-OHDA-lesioned rat model of Parkinson's disease (PD). In PC12 cells, treatment with (-)-sesamin (25 – 50 mM) increased intracellular dopamine levels and enhanced L-DOPA-induced increase in dopamine levels. (-)-Sesamin (25 mM) induced cyclic AMP-dependent kinase A (PKA), cyclic AMP-response element binding protein (CREB), and tyrosine hydroxylase (TH) phosphorylation. (-)-Sesamin (25 mM) also induced transient extracellular signal-regulated kinase (ERK1/2) phosphorylation and Bad phosphorylation at Ser112 (BadSer112) in PC12 cells. In contrast, sustained ERK1/2 phosphorylation, p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK1/2) phosphorylation, and cleaved-caspase-3 activity, which were induced by 6-OHDA (100 mM), were decreased by (-)-sesamin (25 mM) in PC12 cells. These results suggested that (-)-sesamin induced dopamine biosynthesis via the phosphorylation of PKA-CREB-TH system and protected 6-OHDA-induced cytotoxicity via the activation of transient ERK1/2-BadSer112 system and the inhibition of sustained ERK-p38MAPK-JNK1/2-caspase-3 system in PC12 cells. (-)-Sesamin may serve as an adjuvant phytonutrient in PD.
Keywords: Sesamin, ERK, dopamine, Parkinson's disease, PC12 cells
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