| Apoptosis in sulfur mustard treated A549 cell cultures. | |
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MedLine Citation:
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PMID: 17229443 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The chemical warfare agent sulfur mustard (SM) is a strong alkylating agent that leads to erythema and ulceration of the human skin several hours after exposure. Although SM has been intensively investigated, the cellular mechanisms leading to cell damage remain unclear. Apoptosis, necrosis and direct cell damage are discussed. In this study we investigated apoptotic cell death in pulmonary A549 cells exposed to SM (30-1000 microM, 30 min). 24 h after SM exposure DNA breaks were stained with the TUNEL method. Additionally, A549 cells were lysed and cellular protein was transferred to SDS page and blotted. Whole PARP as well as PARP cleavage into the p89 fragment, an indicator of apoptosis, were detected by specific antibodies. SM concentration dependent increase in TUNEL positive cells and PARP cleavage showed that SM is an inducer of apoptosis. It has been previously suggested that AChE is activated during apoptotic processes and may be involved in apoptosis regulation. Therefore, we examined AChE activity in A549 cells upon induction of apoptosis by SM (100-500 microM). Increased AChE activity was found in SM treated A549 cell cultures examined as determined by the Ellman's assay and by western blot. AChE activity showed a strong correlation with TUNEL positive cells. However, the broad caspase inhibitor zVAD and the PARP-inhibitor 3-aminobenzamide had no protective effect on A459 cells measured with AChE activity and frequency of TUNEL positive cells. In summary, our studies demonstrate that AChE activity may be a potential marker of apoptosis in A549 cells after SM injury. To what extent AChE is involved in apoptosis regulation during SM poisoning has to be further investigated. |
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Authors:
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D Steinritz; J Emmler; M Hintz; F Worek; H Kreppel; L Szinicz; K Kehe |
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Publication Detail:
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Type: Journal Article Date: 2006-12-14 |
Journal Detail:
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Title: Life sciences Volume: 80 ISSN: 0024-3205 ISO Abbreviation: Life Sci. Publication Date: 2007 May |
Date Detail:
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Created Date: 2007-06-04 Completed Date: 2007-08-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375521 Medline TA: Life Sci Country: England |
Other Details:
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Languages: eng Pagination: 2199-201 Citation Subset: IM |
Affiliation:
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Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholinesterase
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metabolism Amino Acid Chloromethyl Ketones / pharmacology Apoptosis / drug effects* Benzamides / pharmacology Caspase 3 / antagonists & inhibitors, metabolism Cell Extracts / analysis Cell Line, Tumor Chemical Warfare Agents / pharmacology Cysteine Proteinase Inhibitors / pharmacology Dose-Response Relationship, Drug Electrophoresis, Polyacrylamide Gel Humans Hydrolysis / drug effects Immunoblotting In Situ Nick-End Labeling Mustard Gas / pharmacology* Poly(ADP-ribose) Polymerases / antagonists & inhibitors, chemistry, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/Benzamides; 0/Cell Extracts; 0/Chemical Warfare Agents; 0/Cysteine Proteinase Inhibitors; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 3544-24-9/3-aminobenzamide; 505-60-2/Mustard Gas; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.1.1.7/Acetylcholinesterase; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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