Document Detail


Effects of thimerosal on NGF signal transduction and cell death in neuroblastoma cells.
MedLine Citation:
PMID:  15843506     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Signaling through neurotrophic receptors is necessary for differentiation and survival of the developing nervous system. The present study examined the effects of the organic mercury compound thimerosal on nerve growth factor signal transduction and cell death in a human neuroblastoma cell line (SH-SY5Y cells). Following exposure to 100 ng/ml NGF and increasing concentrations of thimerosal (1 nM-10 microM), we measured the activation of TrkA, MAPK, and PKC-delta. In controls, the activation of TrkA MAPK and PKC-delta peaked after 5 min of exposure to NGF and then decreased but was still detectable at 60 min. Concurrent exposure to increasing concentrations of thimerosal and NGF for 5 min resulted in a concentration-dependent decrease in TrkA and MAPK phosphorylation, which was evident at 50 nM for TrkA and 100 nM for MAPK. Cell viability was assessed by the LDH assay. Following 24-h exposure to increasing concentrations of thimerosal, the EC50 for cell death in the presence or absence of NGF was 596 nM and 38.7 nM, respectively. Following 48-h exposure to increasing concentrations of thimerosal, the EC50 for cell death in the presence and absence of NGF was 105 nM and 4.35 nM, respectively. This suggests that NGF provides protection against thimerosal cytotoxicity. To determine if apoptotic versus necrotic cell death was occurring, oligonucleosomal fragmented DNA was quantified by ELISA. Control levels of fragmented DNA were similar in both the presence and absence of NGF. With and without NGF, thimerosal caused elevated levels of fragmented DNA appearing at 0.01 microM (apoptosis) to decrease at concentrations >1 microM (necrosis). These data demonstrate that thimerosal could alter NGF-induced signaling in neurotrophin-treated cells at concentrations lower than those responsible for cell death.
Authors:
Damani K Parran; Angela Barker; Marion Ehrich
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2005-04-20
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  86     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-06-07     Completed Date:  2005-10-11     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  132-40     Citation Subset:  IM    
Affiliation:
Virginia-Maryland Regional College of Veterinary Medicine, Laboratory for Neurotoxicity Studies, Virginia Tech, 1 Duckpond Drive, Blacksburg, Virginia 24061-0442, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Death / drug effects*
Cell Line, Tumor
Enzyme Activation
Enzyme-Linked Immunosorbent Assay
Humans
Mitogen-Activated Protein Kinases / metabolism
Nerve Growth Factor / metabolism*
Neuroblastoma / enzymology,  metabolism*,  pathology
Phosphorylation
Protein Kinase C / metabolism
Protein Kinase C-delta
Signal Transduction / drug effects*
Thimerosal / toxicity*
Chemical
Reg. No./Substance:
54-64-8/Thimerosal; 9061-61-4/Nerve Growth Factor; EC 2.7.11.13/PRKCD protein, human; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.13/Protein Kinase C-delta; 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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