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L 1 Cell Adhesion Molecule Signaling Is Inhibited by Ethanol In Vivo
Author(s) -
Littner Yoav,
Tang Ningfeng,
He Min,
Bearer Cynthia F.
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2012.01944.x
Subject(s) - dephosphorylation , phosphorylation , neurotoxicity , in vivo , tyrosine phosphorylation , in vitro , signal transduction , tyrosine , ethanol , chemistry , biochemistry , microbiology and biotechnology , biology , toxicity , phosphatase , organic chemistry
Background Fetal alcohol spectrum disorder is an immense public health problem. In vitro studies support the hypothesis that L 1 cell adhesion molecule ( L 1) is a target for ethanol ( EtOH ) developmental neurotoxicity. L 1 is critical for the development of the central nervous system. It functions through signal transduction leading to phosphorylation and dephosphorylation of tyrosines on its cytoplasmic domain. The function of L 1 is also dependent on trafficking through lipid rafts ( LR s). Our hypothesis is that L 1 is a target for EtOH neurotoxicity in vivo. Our objective is to demonstrate changes in L 1 phosphorylation/dephosphorylation and LR association in vivo. Methods Rat pups on postnatal day 6 are administered 4.5, 5.25, and 6 g/kg of EtOH divided into 2 doses 2 hours apart, then killed. Cerebella are rapidly frozen for assay. Blood is analyzed for blood EtOH concentration. L 1 tyrosine phosphorylation is determined by immunoprecipitation and dephosphorylation of tyrosine 1176 determined by immunoblot. LR s are isolated by sucrose density gradient, and the distribution of L 1 in LR s is determined. Results EtOH at all doses reduced the relative amount of Y 1176 dephosphorylation as well as the relative amount of L 1 phosphorylated on other tyrosines. The proportion of L 1 present in LR s is significantly increased in pups who received 6 g/kg EtOH compared to intubated controls. Conclusions L 1 is a target for EtOH developmental neurotoxicity in vivo.