| (+/-)-2-Chloropropionic acid elevates reactive oxygen species formation in human neutrophil granulocytes. | |
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MedLine Citation:
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PMID: 17007989 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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(+/-)-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. |
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Authors:
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B B Aam; F Fonnum |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-09-01 |
Journal Detail:
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Title: Toxicology Volume: 228 ISSN: 0300-483X ISO Abbreviation: Toxicology Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-11-13 Completed Date: 2007-01-04 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0361055 Medline TA: Toxicology Country: Ireland |
Other Details:
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Languages: eng Pagination: 124-34 Citation Subset: IM |
Affiliation:
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Norwegian Defence Research Establishment, Division for Protection, P.O. Box 25, N-2027 Kjeller, Norway. bba@ffi.no <bba@ffi.no> |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acridines
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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:
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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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