Document Detail


Toxic effect of L-2-chloropropionate on cultured rat cerebellar granule cells is ameliorated after inhibition of reactive oxygen species formation.
MedLine Citation:
PMID:  11746428     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oral administration of rats to L-2-chloropropionate (L-CPA) causes selective necrosis to the granule cell layer of the cerebellum in vivo and to cultured rat cerebellar granule cells in vitro. The present study was conducted to characterize the involvement of reactive oxygen species (ROS) in cell death of L-CPA to rat cerebellar granule cells in vitro. Exposure to L-CPA (0.625-10 mM) produced a concentration dependent increase in formation of 2,7-dichlorofluorescein (DCF) as a measure of formation of ROS. The elevation of ROS was inhibited after incubation of the cells with the ERK-type of MAP kinases inhibitor U0126, the mitochondrial permeability transition pore inhibitor cyclosporin A (CSA), the antioxidant vitamin E, and the spin trap N-tert-butyl-alpha-(2-sulfophenyl)-nitrone (S-PBN). Measurements of nitrite (NO(2)) in the cell culture supernatant using the Griess reagent indicate generation of nitric oxide (NO) after exposure to L-CPA. Incubation with L-CPA (10 mM) for 48 hr lead to cell death (90%). When the granule cells were incubated with L-CPA in combination with the inhibitors of free radical production, the cell death was ameliorated. The results show that L-CPA is toxic to granular cells by production of ROS.
Authors:
O Myhre; B Bjugan; F Fonnum
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  66     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2001 Dec 
Date Detail:
Created Date:  2001-12-17     Completed Date:  2002-02-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  992-7     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Wiley-Liss, Inc.
Affiliation:
Norwegian Defence Research Establishment, Division for Protection and Materiel, PO Box 25, N-2027 Kjeller, Norway. oddvar.myhre@ffi.no
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Antioxidants / pharmacology
Cell Death / drug effects,  physiology*
Cells, Cultured
Cerebellar Cortex / drug effects*,  metabolism,  physiopathology
Enzyme Inhibitors / pharmacology
Glutathione / drug effects,  metabolism
Immunosuppressive Agents / pharmacology
Intracellular Membranes / drug effects,  metabolism
Mitochondria / drug effects,  metabolism
Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
Neurons / drug effects*,  metabolism
Neuroprotective Agents / pharmacology
Neurotoxins / toxicity*
Oxidative Stress / drug effects,  physiology*
Permeability / drug effects
Propionic Acids / toxicity*
Rats
Rats, Wistar
Reactive Oxygen Species / antagonists & inhibitors*,  metabolism
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Enzyme Inhibitors; 0/Immunosuppressive Agents; 0/Neuroprotective Agents; 0/Neurotoxins; 0/Propionic Acids; 0/Reactive Oxygen Species; 598-78-7/2-chloropropionic acid; 70-18-8/Glutathione; EC 2.7.11.24/Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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