CHOLINE AMELIORATES ETHANOL INDUCED ALTERATIONS IN TYROSINE PHOSPHORYLATION AND DISTRIBUTION IN DETERGENT-RESISTANT MEMBRANE MICRODOMAINS OF L1 CELL ADHESION MOLECULE IN VIVO
| Autor: | Daniel Lee, Natalie L. Davis, Ningfeng Tang, Cynthia F. Bearer, Min He |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Embryology medicine.medical_specialty Health Toxicology and Mutagenesis Detergents Neural Cell Adhesion Molecule L1 030105 genetics & heredity Toxicology Article Choline Dephosphorylation 03 medical and health sciences chemistry.chemical_compound Membrane Microdomains In vivo Pregnancy Internal medicine medicine Animals Phosphorylation Lipid raft Ethanol Chemistry Tyrosine phosphorylation Rats 030104 developmental biology Endocrinology Pediatrics Perinatology and Child Health Toxicity Tyrosine Female Developmental Biology |
| Zdroj: | Birth Defects Res |
| Popis: | Background Exposure to ethanol during pregnancy is the cause of fetal alcohol spectrum disorder. The function of L1 cell adhesion molecule (L1), critical for proper brain development, is dependent on detergent-resistant membrane microdomains (DRM). Ethanol at low concentrations disrupts L1 function measured by inhibition of downstream signaling and alterations in L1-DRM distribution in cerebellum in vivo and in cerebellar granule neurons (CGN) in vitro. We have previously shown that choline pretreatment of CGN partially prevents ethanol toxicity through improving L1 function in vitro. Here we show that choline supplementation reduces the impact of ethanol on L1 in cerebellum in vivo. Methods Pregnant rat dams were placed on choline free diet on gestational Day 5 (G5). Pups were treated with saline or choline from postnatal day (P) 1-5. On P5, pups were intubated twice 2 hr apart with ethanol or Intralipid® for a total dose of 6 g/kg/d and sacrificed 1 hr after the last intubation. The cerebella were harvested and L1 phosphorylation/dephosphorylation status and distribution in DRM were analyzed. Results Ethanol reduced L1 tyrosine phosphorylation and L1-Y1176 dephosphorylation in cerebella, and caused an increase in the percent of L1 in DRM. Choline supplementation of pups reduced the ethanol-induced changes in L1 phosphorylation status and ameliorated ethanol-induced redistribution of L1 into DRM. Conclusion Choline supplementation before an acute dose of ethanol ameliorates changes in L1 in vivo. |
| Databáze: | OpenAIRE |
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