| Mechanism of Pyrethroid Pesticide-Induced Apoptosis: Role of Calpain and the ER Stress Pathway. | |
| | |
MedLine Citation:
|
PMID: 21555338 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Exposure to the pyrethroid pesticide deltamethrin has been demonstrated to cause apoptosis both in vitro and in vivo. However, the molecular pathways leading to deltamethrin-induced apoptosis have not been established. To identify these pathways, SK-N-AS neuroblastoma cells were exposed to deltamethrin (100 nM-5 μM) for 24-48 hrs. Deltamethrin produced a time and dose-dependent increase (21-121%) in DNA fragmentation, an indicator of apoptosis. Data demonstrate that the initiation of DNA fragmentation resulted from interaction of deltamethrin with Na(+) channels and consequent calcium influx, as tetrodotoxin and the intracellular Ca(2+) chelator BAPTA-AM completely prevented apoptosis. DNA fragmentation was accompanied by increased caspase-9 and 3 activities, and was abolished by specific caspase-9 and 3 inhibitors. However, deltamethrin did not increase cytosolic cytochrome c levels, indicating that the mitochondrial pathway was likely not involved. Additional studies demonstrated that deltamethrin exposure activated caspase-12 activity, and that pharmacological inhibition and siRNA knockdown of calpain, prevented deltamethrin-induced DNA fragmentation, thus indicating a role for the ER stress pathway. This was confirmed by the observation that inhibition of eIF2α abolished deltamethrin-induced DNA fragmentation. Together, these data demonstrate that deltamethrin causes apoptosis through its interaction with Na(+) channels, leading to calcium overload and activation of the ER stress pathway. Because ER stress and the subsequent unfolded protein response have been observed in a number of neurodegenerative diseases, these data provide mechanistic information by which high level exposure to pyrethroids may contribute to neurodegeneration. |
| | |
Authors:
|
Muhammad M Hossain; Jason R Richardson |
Related Documents
:
|
18295348 - Tlr2 and tlr4 expression on the immune cells of tuberculous pleural fluid. 15265938 - Different domains of pseudomonas aeruginosa exoenzyme s activate distinct tlrs. 20798608 - Traf6 and a20 differentially regulate tlr4-induced autophagy by affecting the ubiquitin... 16338228 - A molecule that is associated with toll-like receptor 4 and regulates its cell surface ... 15994108 - In vivo efficiency of targeted norfloxacin against persistent, isoniazid-insensitive, m... 22008998 - Glucocorticoid receptor antagonist sensitizes trail-induced apoptosis in renal carcinom... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-5-9 |
Journal Detail:
|
Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: - ISSN: 1096-0929 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
|
Created Date: 2011-5-10 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9805461 Medline TA: Toxicol Sci Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, and Environmental and Occupational Health Sciences Institute, Piscataway, NJ 08854, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The Incorporation Of Lysine Into The Peroxidase Peptide Reactivity Assay For Skin Sensitization Asse...
Next Document: Effectiveness of cognitive behavioural therapy in primary health care: a review.