TOLUENE DISRUPTION OF THE FUNCTIONS OF L1 CELL ADHESION MOLECULE AT CONCENTRATIONS ASSOCIATED WITH OCCUPATIONAL EXPOSURES
| Autor: | Ningfeng Tang, Min He, Kimberly White, Cynthia F. Bearer, Natalie L. Davis, Julia A. Sabatino |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Neurite Fetal alcohol syndrome Neural Cell Adhesion Molecule L1 Biology Article Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Membrane Microdomains Laminin Pregnancy Occupational Exposure medicine Neurites Animals Phosphorylation Extracellular Signal-Regulated MAP Kinases Lipid raft Neurons Fetus Neurogenesis medicine.disease Molecular biology Toluene 3. Good health Rats 030104 developmental biology Biochemistry chemistry Maternal Exposure Prenatal Exposure Delayed Effects Pediatrics Perinatology and Child Health biology.protein Female 030217 neurology & neurosurgery |
| Zdroj: | Pediatric research |
| ISSN: | 1530-0447 0031-3998 |
| Popis: | 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 (1) toluene inhibits L1-mediated NOG and (2) 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 hours 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. |
| Databáze: | OpenAIRE |
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