title: Modulatory effects of sesamin on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells.
abstract: The effects of sesamin on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Sesamin at concentration ranges of 20-75 μM exhibited a significant increase in intracellular dopamine levels at 24 h: 50 μM sesamin increased dopamine levels to 133% and tyrosine hydroxylase (TH) activity to 128.2% of control levels. Sesamin at 20-100 μM rapidly increased the intracellular levels of cyclic AMP (cAMP) to 158.3%-270.3% of control levels at 30 min. At 50 μM, sesamin combined with L-DOPA (50, 100 and 200 μM) further increased the intracellular dopamine levels for 24 h compared to L-DOPA alone. In the absence or presence of L-DOPA (100 and 200 μM), sesamin (50 μM) increased the phosphorylation of TH, cAMP-dependent protein kinase (PKA), and cAMP-response element-binding protein (CREB), as well as the mRNA levels of TH and CREB for 24 h, an effect which was reduced by L-DOPA (100 and 200 μM). In addition, 50 μM sesamin exhibited a protective effect against L-DOPA (100 and 200 μM)-induced cytotoxicity via the inhibition of reactive oxygen species (ROS) production and superoxide dismutase reduction, induction of extracellular signal-regulated kinase (ERK)1/2 and BadSer112 phosphorylation and Bcl-2 expression, and inhibition of cleaved-caspase-3 formation. These results suggested that sesamin enhanced dopamine biosynthesis and L-DOPA-induced increase in dopamine levels by inducing TH activity and TH gene expression, which was mediated by cAMP-PKA-CREB systems. Sesamin also protected against L-DOPA (100-200 μM)-induced cytotoxicity through the suppression of ROS activity via the modulation of ERK1/2, BadSer112, Bcl-2, and caspase-3 pathways in PC12 cells. Therefore, sesamin might serve as an adjuvant phytonutrient for neurodegenerative diseases.
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 52, Naesudong-ro, Heungduk-gu, Cheongju 361-763, Republic of Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Hak Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Keun Hong
authors.initials: KH
authors.lastname: Park
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Choi
authors.forename: Sung Cil
authors.initials: SC
authors.lastname: Lim
authors.forename: Myung Koo
authors.initials: MK
authors.lastname: Lee
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003603:Cytotoxins / Q000633:toxicity*; D004149:Dioxoles / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D007980:Levodopa / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017705:Lignans / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D012639:Seeds; D031685:Sesamum
chemical_list: D003603:Cytotoxins; D004149:Dioxoles; D017705:Lignans; D017382:Reactive Oxygen Species; D007980:Levodopa; C054125:sesamin; D004298:Dopamine