title: Curcumin-Protected PC12 Cells Against Glutamate-Induced Oxidative Toxicity.
abstract: Glutamate is a major excitatory neurotransmitter present in the central nervous system. The glutamate/cystine antiporter system xc-connects the antioxidant defense with neurotransmission and behaviour. Overactivation of ionotropic glutamate receptors induces neuronal death, a pathway called excitotoxicity. Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases including cerebral ischemia, Alzheimer's and Huntington's disease. Curcuma has a wide spectrum of biological activities regarding neuroprotection and neurocognition. By reducing the oxidative damage, curcumin attenuates a spinal cord ischemia-reperfusion injury, seizures and hippocampal neuronal loss. The rat pheochromocytoma (PC12) cell line exhibits many characteristics useful for the study of the neuroprotection and neurocognition. This investigation was carried out to determine whether the neuroprotective effects of curcumin can be observedviathe glutamate-PC12 cell model. Results indicate that glutamate (20 mM) upregulated glutathione peroxidase 1, glutathione disulphide, Ca2+influx, nitric oxide production, cytochrome c release, Bax/Bcl-2 ratio, caspase-3 activity, lactate dehydrogenase release, reactive oxygen species, H2O2, and malondialdehyde; and downregulated glutathione, glutathione reductase, superoxide dismutase and catalase, resulting in enhanced cell apoptosis. Curcumin alleviates all these adverse effects. Conclusively, curcumin can effectively protect PC12 cells against the glutamate-induced oxidative toxicity. Its mode of action involves two pathways: the glutathione-dependent nitric oxide-reactive oxygen species pathway and the mitochondria-dependent nitric oxide-reactive oxygen species pathway.
authors.affiliation: Research Institute of Biotechnology, Hungkuang University, 34 Chung-Chie Rd., Shalu County, Taichung City 43022, Taiwan.
authors.forename: Chi-Huang
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Pharmacy, Kuang-Tieng General Hospital, Shalu County, Taichung City 43302, Taiwan.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Chen
authors.affiliation: Research Institute of Biotechnology, Hungkuang University, 34 Chung-Chie Rd., Shalu County, Taichung City 43022, Taiwan.
authors.forename: George
authors.initials: G
authors.lastname: Yü
authors.affiliation: Graduate Institute of Clinical Medicine, Taipei Medical University, 250 Wu-Xing St., Taipei 10031, Taiwan.
authors.forename: Chiung-Chi
authors.initials: CC
authors.lastname: Peng
authors.affiliation: Research Institute of Biotechnology, Hungkuang University, 34 Chung-Chie Rd., Shalu County, Taichung City 43022, Taiwan; Research Institute of Medical Sciences, Taipei Medical University, 250 Wu-Xing St., Taipei 10031, Taiwan.
authors.forename: Robert Y
authors.initials: RY
authors.lastname: Peng
keywords: PC12 cell line; apoptotic pathways; caspase; curcumin; glutamate cytotoxicity; glutathione; nitric oxide; reactive oxidative substances