Peptide Antagonists of Ethanol Inhibition of L1-Mediated Cell-Cell Adhesion

@article{Wilkemeyer2002PeptideAO,
  title={Peptide Antagonists of Ethanol Inhibition of L1-Mediated Cell-Cell Adhesion},
  author={Michael F. Wilkemeyer and Carrie E Menkari and Catherine Y. Spong and Michael E. Charness},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2002},
  volume={303},
  pages={110 - 116}
}
Ethanol inhibits cell-cell adhesion mediated by the L1 cell adhesion molecule. 1-Octanol potently antagonizes this cellular action of ethanol and also prevents ethanol-induced dysmorphology and cell death in mouse whole embryo culture. NAPVSIPQ (NAP) and SALLRSIPA (SAL) are active peptide fragments of two neuroprotective proteins: activity-dependent neuroprotective protein and activity-dependent neurotrophic factor. NAP and SAL are neuroprotective at femtomolar concentrations against a variety… Expand
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References

SHOWING 1-10 OF 48 REFERENCES
Novel antagonists of alcohol inhibition of l1-mediated cell adhesion: multiple mechanisms of action.
TLDR
It is suggested that selective straight, branched, and cyclic alcohols may act at multiple, discrete sites to antagonize the actions of ethanol and 1-butanol on L1-mediated cell-cell adhesion. Expand
Ethanol inhibits neural cell-cell adhesion.
TLDR
It is shown that concentrations of ethanol achieved during social drinking inhibit hOP-1-induced cell clustering without affecting cell proliferation, the induction and cell surface expression of N-CAM and L1, or the alternative splicing and sialylation of N -CAM. Expand
Antagonists of alcohol inhibition of cell adhesion.
TLDR
Notably strict structural requirements for alcohol inhibition of cell-cell adhesion are demonstrated in L1-transfected NIH 3T3 fibroblasts and in NG108-15 neuroblastoma x glioma hybrid cells treated with BMP-7, an inducer of L1 and neural cell adhesion molecule. Expand
Alcohol inhibition of cell adhesion in BMP-treated NG108-15 cells.
TLDR
These data suggest that ethanol inhibits cell-cell adhesion in OP-1-treated NG108-15 cells by interacting directly or indirectly with the neuronal isoform of L1. Expand
Ethanol Inhibits L1-mediated Neurite Outgrowth in Postnatal Rat Cerebellar Granule Cells*
TLDR
One mechanism of ethanol’s toxicity to the developing central nervous system may be the inhibition of L1-mediated neurite outgrowth, which is similar to those of patients with mutations in L1, a neural cell adhesion molecule. Expand
Alcohol inhibits cell-cell adhesion mediated by human L1 [published erratum appears in J Cell Biol 1996 Jun;133(5):1139-40]
TLDR
Because L1 plays a role in both neural development and learning, ethanol inhibition of L1-mediated cell-cell interactions could contribute to FAS and ethanol-associated memory disorders. Expand
Characterization of Ethanol‐Sensitive and Insensitive Fibroblast Cell Lines Expressing Human L1
TLDR
It is shown that ethanol inhibits L1‐mediated cell‐cell adhesion in fibroblast cell lines stably transfected with human L1, suggesting that L1 may exist in an alcohol‐sensitive or an alcohol-insensitive state that may be governed by host cell factors. Expand
Induction of the neural cell adhesion molecule and neuronal aggregation by osteogenic protein 1.
TLDR
HOP-1 produces morphologic changes in NG108-15 cells, at least in part, by inducing N-CAM, and observations suggest that OP-1 or a homologue may participate in the regulation of N- CAM during nervous system development and regeneration. Expand
Osteogenic protein-1 regulates L1 and neural cell adhesion molecule gene expression in neural cells.
TLDR
It is shown that hOP-1 induces L1 expression approximately 6-fold in NG108-15 cells without changing the levels of N-cadherin, neurofilament 200, Thy-1, tau, and G alpha s, which is the first described growth factor that regulates both N-CAM and L1 gene expression. Expand
A femtomolar-acting neuroprotective peptide induces increased levels of heat shock protein 60 in rat cortical neurons: a potential neuroprotective mechanism
TLDR
It was now shown that ADNF-9 increased the expression of heat shock protein 60 (hsp60) in rat cerebral cortical cultures, and the protection against the beta-amyloid peptide-associated cell death may be mediated in part by intracellular increases in hsp60. Expand
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3
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5
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