Fucoidan attenuates 6-hydroxydopamine-induced neurotoxicity by exerting anti-oxidative and anti-apoptotic actions in SH-SY5Y cells |
Myung-Hwan Kim1, Hoon Namgoong1, Bae-Dong Jung1, Myung-Sang Kwon1, Yeon-Shik Choi2, Taekyun Shin3, Hyoung-Chun Kim4, Myung-Bok Wie1 |
1College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University 2Department of Laboratory Animal Science, Korea Biopolytechnic College 3College of Veterinary Medicine, Jeju National University 4College of Pharmacy, Kangwon National University |
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Abstract |
Parkinson's disease (PD) is an irreversible neurological disorder with related locomotor dysfunction and is characterized by the selective loss of nigral neurons. PD can be experimentally induced by 6-hydroxydopamine (6-OHDA). It has been reported that reactive oxygen species, which deplete endogenous glutathione (GSH) levels, may play important roles in the dopaminergic cell death characteristic of PD. Fucoidan, a sulfated algal polysaccharide, exhibits anti-inflammatory and anti-oxidant actions. In this study, we investigated whether fucoidan can protect against 6-OHDA-mediated cytotoxicity in SH-SY5Y cells. Cytotoxicity was evaluated by using MTT and LDH assays. Fucoidan alleviated cell damage evoked by 6-OHDA dose-dependently. Fucoidan reduced the number of apoptotic nuclei and the extent of annexin-V-associated apoptosis, as revealed by DAPI staining and flow cytometry. Elevation of lipid peroxidation and caspase-3/7 activities induced by 6-OHDA was attenuated by fucoidan, which also protected against cytotoxicity evoked by buthionine-sulfoximine-mediated GSH depletion. Reduction in the glutathione/glutathione disulfide ratio induced by 6-OHDA was reversed by fucoidan, which also inhibited 6-OHDA-induced disruption of mitochondrial membrane potential. The results indicate that fucoidan may have protective action against 6-OHDA-mediated neurotoxicity by modulating oxidative injury and apoptosis through GSH depletion. |
Key Words:
apoptosis, caspase-3/7, fucoidan, glutathione/glutathione disulfide ratio, 6-hydroxydopamine |
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