https://scholars.lib.ntu.edu.tw/handle/123456789/564603
標題: | Protection of dopaminergic neurons by 5-lipoxygenase inhibitor | 作者: | Kang K.-H. HORNG-HUEI LIOU Hour M.-J. Liou H.-C. WEN-MEI FU |
公開日期: | 2013 | 卷: | 73 | 起(迄)頁: | 380-387 | 來源出版物: | Neuropharmacology | 摘要: | Neuroinflammation and oxidative stress are important factors that induce neurodegeneration in age-related neurological disorders. 5-Lipoxygenase (5-LOX) is the enzyme responsible for catalysing the synthesis of leukotriene or 5-HETE from arachidonic acid. 5-LOX is expressed in the central nervous system and may cause neurodegenerative disease. In this study, we investigated the effect of the pharmacological inhibition of 5-lipoxygenase on 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)/MPP+-induced dopaminergic neuronal death in midbrain neuroneglia co-cultures and in mice. It was found that 5-LOX was over-expressed in astrocytes after the injection of MPTP into C57BL6 mice. MK-886, a specific inhibitor of 5-LOX activating protein (FLAP), significantly increased [3H]-dopamine uptake, a functional indicator of the integrity of dopaminergic neurons, in midbrain cultures or the SH-SY5Y human dopaminergic cell line following MPP+ treatment. In addition, LTB4, one of 5-LOX's downstream products, was increased in the striatum and substantia nigra following MPTP injection in mice. LTB4 but not LTD4 and 5-HETE enhanced MPP+-induced neurotoxicity in primary midbrain cultures. MK-886 administration increased the number of tyrosine hydroxylase-positive neurons in the substantia nigra and the dopamine content in the striatum in MPTP-induced parkinsonian mice. Furthermore, the MPTP-induced upregulation of LTB4 in the striatum and substantia nigra was antagonised by MK-886. These results suggest that 5-LOX inhibitors may be developed as novel neuroprotective agents and LTB4 may play an important pathological role in Parkinson's disease. ? 2013 Elsevier Ltd. All rights reserved. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/564603 | ISSN: | 283908 | DOI: | 10.1016/j.neuropharm.2013.06.014 | SDG/關鍵字: | lipoxygenase inhibitor; animal experiment; animal model; article; astrocyte; brain region; cell survival; controlled study; corpus striatum; dopaminergic nerve cell; drug efficacy; drug mechanism; drug response; glia; human; human cell; mesencephalon; mouse; nerve cell necrosis; neuroprotection; neurotoxicity; nonhuman; Parkinson disease; priority journal; protein expression; substantia nigra; upregulation; 5-Lipoxygenase; FLAP; MK-886; Parkinson's disease; 5-Lipoxygenase-Activating Protein Inhibitors; 5-Lipoxygenase-Activating Proteins; Animals; Arachidonate 5-Lipoxygenase; Astrocytes; Cell Death; Coculture Techniques; Corpus Striatum; Dopamine; Dopaminergic Neurons; Humans; Hydroxyeicosatetraenoic Acids; Indoles; Leukotriene B4; Leukotriene D4; Male; Mesencephalon; Mice; MPTP Poisoning; Neuroprotective Agents; Substantia Nigra |
顯示於: | 藥理學科所 |
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