RGD Reference Report - Toluene disruption of the functions of L1 cell adhesion molecule at concentrations associated with occupational exposures. - Rat Genome Database

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Toluene disruption of the functions of L1 cell adhesion molecule at concentrations associated with occupational exposures.

Authors: White, Kimberly M R  Sabatino, Julia A  He, Min  Davis, Natalie  Tang, Ningfeng  Bearer, Cynthia F 
Citation: White KM, etal., Pediatr Res. 2016 Jul;80(1):145-50. doi: 10.1038/pr.2016.40. Epub 2016 Mar 8.
RGD ID: 401959323
Pubmed: PMID:27027721   (View Abstract at PubMed)
PMCID: PMC4929035   (View Article at PubMed Central)
DOI: DOI:10.1038/pr.2016.40   (Journal Full-text)


BACKGROUND: Prenatal toluene exposure can cause neurodevelopmental disabilities similar to fetal alcohol syndrome. Both share neuroanatomic pathologies similar to children with mutations in L1 cell adhesion molecule (L1). L1 mediates neurite outgrowth (NOG) via signaling through ERK1/2, which require trafficking of L1 through lipid rafts. Our objective is to determine if toluene inhibits L1-mediated NOG and toluene inhibits L1 signaling at concentrations achieved during occupational exposure.
METHODS: Concentrations of toluene reflective of blood concentrations achieved in solvent abusers and occupational settings are used. Cerebellar granule neurons (CGN) harvested from postnatal day 6 rat pups are plated on coverslips coated with poly-L-lysine (PLL) alone or PLL followed by laminin. L1 is added to the media of CGN plated on PLL alone. Toluene is added 2 h after plating. Cells are fixed at 24 h and neurite length is measured. ERK1/2 activation by L1 in CGN is analyzed by immunoblot.
RESULTS: Toluene significantly reduced mean neurite length of CGN exposed to L1 but not laminin. Toluene significantly reduced L1-mediated ERK1/2 phosphorylation.
CONCLUSION: Results suggest that toluene inhibits L1-lipid raft interactions at occupationally relevant concentrations and may lead to a fetal solvent spectrum disorder similar to fetal alcohol spectrum disorder.



Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
L1CAMHumantoluene decreases phosphorylationISOL1cam (Rattus norvegicus)toluene decreases phosphorylation of ERK1/2 by L1CAM in isolated rat cerebellar granule neuronsRGD 
L1camMousetoluene decreases phosphorylationISOL1cam (Rattus norvegicus)toluene decreases phosphorylation of ERK1/2 by L1CAM in isolated rat cerebellar granule neuronsRGD 
L1camRattoluene decreases phosphorylationEXP toluene decreases phosphorylation of ERK1/2 by L1CAM in isolated rat cerebellar granule neuronsRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
L1camRatcerebellar neuron development  IMP  RGD 
L1camRatprotein localization to plasma membrane raft  IDA bioassay MMO:0000441RGD 
L1camRatregulation of neuron projection development  IMP  RGD 
L1camRatregulation of protein phosphorylation  IMP  RGD 
L1camRatresponse to toluene  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
L1cam  (L1 cell adhesion molecule)

Genes (Mus musculus)
L1cam  (L1 cell adhesion molecule)

Genes (Homo sapiens)
L1CAM  (L1 cell adhesion molecule)


Additional Information