Effects of (-)-sesamin on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and dopaminergic neuronal cells of Parkinson's disease rat models.

Abstract

The present study investigated the effects of (-)-sesamin on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity using PC12 cells and dopaminergic neuronal cells of 6-OHDA-lesioned rat model of Parkinson's disease (PD). In PC12 cells, treatment with (-)-sesamin (25 µM) reduced 6-OHDA (100 µM)-induced cell death and induced transient extracellular signal-regulated kinase (ERK1/2) phosphorylation and Bad phosphorylation at Ser112 (BadSer112). 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, all of which were induced by 6-OHDA (100 µM), were inhibited by treatment with (-)-sesamin (25 µM). Furthermore, co-treatment with (-)-sesamin (30 mg/kg, p.o.) once a day for 28 days significantly increased the number of tyrosine hydroxylase-immunopositive neuronal cells and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the substantia nigra-striatum of 6-OHDA-lesioned rat model of PD with or without L-DOPA treatment. These results suggest that (-)-sesamin protects 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 also shows protective effects on long-term L-DOPA therapy in dopaminergic neuronal cells of PD rat models. (-)-Sesamin may serve as adjuvant therapeutics in PD.

• Authors: Hyun Jin Park, Ting Ting Zhao, Kyung Sook Lee, Seung Ho Lee, Keon Sung Shin, Keun Hong Park, Hyun Sook Choi, Myung Koo Lee
• Journal: Neurochemistry international (Neurochem Int) 2015 Apr-May Vol. 83-84 Pg. 19-27 ISSN: 1872-9754 [Electronic] England
• PMID: 25747493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Dioxoles
• Lignans
• Oxidopamine
• Extracellular Signal-Regulated MAP Kinases
• sesamin
• Dopamine

Topics

• Animals
• Cell Survival (drug effects)
• Dioxoles (pharmacology)
• Disease Models, Animal
• Dopamine (metabolism)
• Dopaminergic Neurons (drug effects, metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Lignans (pharmacology)
• Oxidopamine (pharmacology)
• PC12 Cells (drug effects)
• Parkinson Disease (metabolism)
• Rats
• Substantia Nigra (drug effects)