Induction of microglial reactive oxygen species production by the organochlorinated pesticide dieldrin.

作者: Haoyu Mao , Xi Fang , Katon M. Floyd , Jeanette E. Polcz , Ping Zhang

DOI: 10.1016/J.BRAINRES.2007.10.020

关键词: MicrogliaDieldrinEndocrinologyDopaminergicReactive oxygen speciesCell biologyNeurodegenerationBiologyNeurogliaInternal medicineSubstantia nigraNADPH oxidase

摘要: Exposure to pesticides has been speculated contribute the development of sporadic Parkinson's disease (PD) characterized by a progressive degeneration nigrostriatal dopaminergic pathway. Activation brain microglia that produce various neurotoxic factors including cytokines and reactive oxygen species (ROS) increasingly associated with neurodegeneration induced toxicants. Dieldrin, highly persistent organochlorinated pesticide found enriched in substantia nigra some postmortem PD brains, shown be toxic dopamine neurons. In this study, we set out determine effect dieldrin on production ROS underlying mechanism action murine microglia. Treatment microglial cells 0.1 nM 1 microM for 24 h resulted concentration-dependent generation ROS. The dieldrin-induced was time-dependent significant observed 12-24 h, but not 6 after treatment. Furthermore, significantly reduced inhibitors NADPH oxidase, gene transcription protein synthesis. addition immortalized cells, primary microglia, astroglia. These results demonstrate nanomolar concentrations can stimulate may neurons known vulnerable oxidative damage. findings provide important information potential role relevance idiopathic PD.

参考文章(41)
Francesca Aloisi, The role of microglia and astrocytes in CNS immune surveillance and immunopathology. Advances in Experimental Medicine and Biology. ,vol. 468, pp. 123- 133 ,(1999) , 10.1007/978-1-4615-4685-6_10
P S Whitton, Inflammation as a causative factor in the aetiology of Parkinson's disease. British Journal of Pharmacology. ,vol. 150, pp. 963- 976 ,(2007) , 10.1038/SJ.BJP.0707167
J.Timothy Greenamyre, Gillian MacKenzie, Tsung-I Peng, Stacy E. Stephans, Mitochondrial Dysfunction in Parkinson’s Disease Biochemical Society Symposia. ,vol. 66, pp. 85- 97 ,(1999) , 10.1042/BSS0660085
Jau-Shyong Hong, Bin Liu, Lina Du, Naloxone Protects Rat Dopaminergic Neurons against Inflammatory Damage through Inhibition of Microglia Activation and Superoxide Generation Journal of Pharmacology and Experimental Therapeutics. ,vol. 293, pp. 607- 617 ,(2000)
Peter Jenner, C. Warren Olanow, Understanding cell death in Parkinson's disease Annals of Neurology. ,vol. 44, ,(1998) , 10.1002/ANA.410440712
H. M. Sobell, Actinomycin and DNA transcription Proceedings of the National Academy of Sciences of the United States of America. ,vol. 82, pp. 5328- 5331 ,(1985) , 10.1073/PNAS.82.16.5328
D.-C. Wu, P. Teismann, K. Tieu, M. Vila, V. Jackson-Lewis, H. Ischiropoulos, S. Przedborski, NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease Proceedings of the National Academy of Sciences of the United States of America. ,vol. 100, pp. 6145- 6150 ,(2003) , 10.1073/PNAS.0937239100
Jaime M Hatcher, Jason R Richardson, Thomas S Guillot, Alison L McCormack, Donato A Di Monte, Dean P Jones, Kurt D Pennell, Gary W Miller, None, Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system Experimental Neurology. ,vol. 204, pp. 619- 630 ,(2007) , 10.1016/J.EXPNEUROL.2006.12.020
Kim Tieu, Harry Ischiropoulos, Serge Przedborski, Nitric oxide and reactive oxygen species in Parkinson's disease. Iubmb Life. ,vol. 55, pp. 329- 335 ,(2003) , 10.1080/1521654032000114320