Document Detail


(+/-)-2-Chloropropionic acid elevates reactive oxygen species formation in human neutrophil granulocytes.
MedLine Citation:
PMID:  17007989     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
(+/-)-2-Chloropropionic acid (2-CPA) is a neurotoxic compound which kills cerebellar granule cells in vivo, and makes cerebellar granule cells in vitro produce reactive oxygen species (ROS). We have studied the effect of 2-CPA on ROS formation in human neutrophil granulocytes in vitro. We found an increased formation of ROS after 2-CPA exposure using three different methods; the fluorescent probe DCFH-DA and the chemiluminescent probes lucigenin and luminol. Four different inhibitors of ROS formation were tested on the cells in combination with 2-CPA to characterize the signalling pathways. The spin-trap s-PBN, the ERK1/2 inhibitor U0126 and the antioxidant Vitamin E inhibited the 2-CPA-induced ROS formation completely, while the mitochondrial transition permeability pore blocker cyclosporine A inhibited the ROS formation partly. We also found that 2-CPA induced an increased nitric oxide production in the cells by using the Griess reagent. The level of reduced glutathione, measured with the DTNB assay, was decreased after exposure to high concentrations of 2-CPA. Western blotting analysis showed that 2-CPA exposure led to an elevated phosphorylation of ERK MAP kinase. This phosphorylation was inhibited by U0126. Based on these experiments it seems like the mechanisms for 2-CPA induced toxicity involves ROS formation and is similar in neutrophil granulocytes as earlier shown in cerebellar granule cells. This also implies that 2-CPA may be immunotoxic.
Authors:
B B Aam; F Fonnum
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-09-01
Journal Detail:
Title:  Toxicology     Volume:  228     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-13     Completed Date:  2007-01-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  124-34     Citation Subset:  IM    
Affiliation:
Norwegian Defence Research Establishment, Division for Protection, P.O. Box 25, N-2027 Kjeller, Norway. bba@ffi.no <bba@ffi.no>
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MeSH Terms
Descriptor/Qualifier:
Acridines / diagnostic use
Blotting, Western
Cell Separation
Dithionitrobenzoic Acid / metabolism
Extracellular Signal-Regulated MAP Kinases / metabolism
Fluoresceins
Fluorescent Dyes
Glutathione / metabolism
Granulocytes / drug effects,  metabolism*
Humans
Indicators and Reagents
L-Lactate Dehydrogenase / metabolism
Luminescence
Luminol / diagnostic use
Neutrophils / drug effects,  metabolism*
Nitrates / metabolism
Nitrites / metabolism
Propionic Acids / antagonists & inhibitors,  toxicity*
Reactive Oxygen Species / metabolism*
Signal Transduction / drug effects
Sulfhydryl Reagents
Up-Regulation / drug effects
Chemical
Reg. No./Substance:
0/Acridines; 0/Fluoresceins; 0/Fluorescent Dyes; 0/Indicators and Reagents; 0/Nitrates; 0/Nitrites; 0/Propionic Acids; 0/Reactive Oxygen Species; 0/Sulfhydryl Reagents; 2044-85-1/diacetyldichlorofluorescein; 2315-97-1/10,10'-dimethyl-9,9'-biacridinium; 521-31-3/Luminol; 598-78-7/2-chloropropionic acid; 69-78-3/Dithionitrobenzoic Acid; 70-18-8/Glutathione; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases

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


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