JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wilkemeyer, M. F.
Right arrow Articles by Charness, M. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wilkemeyer, M. F.
Right arrow Articles by Charness, M. E.

Vol. 303, Issue 1, 110-116, October 2002

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

Michael F. Wilkemeyer, Carrie E. Menkari, Catherine Y. Spong and Michael E. Charness

Neurology Service, Veterans Administration Boston Healthcare System, West Roxbury, Massachusetts; Department of Neurology, Harvard Medical School, Boston, Massachusetts; Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (M.F.W., C.E.M., M.E.C.); and Section on Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (C.Y.S.)

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 of neurotoxins and also prevent ethanol teratogenesis in mice. To explore the cellular basis for this action, we asked whether NAP and SAL antagonize ethanol inhibition of L1 adhesion. Aggregation assays were carried out in ethanol-sensitive, human L1-transfected NIH/3T3 cells in the absence and presence of NAP and SAL. Neither NAP nor SAL altered L1 adhesion or L1 expression; however, both peptides potently and completely antagonized the inhibition of L1 adhesion by 100 mM ethanol (EC50: NAP, 6 × 10-14 M; SAL, 4 × 10-11 M). NAP also antagonized ethanol inhibition of cell-cell adhesion in bone morphogenetic protein-7-treated NG108-15 cells. In L1-expressing NIH/3T3 cells, SAL antagonism was reversible and could be overcome by increasing concentrations of ethanol. In contrast, NAP antagonism was irreversible and could not be overcome by increasing agonist concentration. Two scrambled NAP peptides (ASPNQPIV and PNIQVASP) were not antagonists at concentrations as high as 10-7 M. Thus, two structurally unrelated classes of compounds, alcohols and small polypeptides, share two common actions: antagonism of ethanol inhibition of L1-mediated cell adhesion and prevention of ethanol teratogenesis. These findings support the hypothesis that ethanol inhibition of L1 adhesion contributes to ethanol teratogenesis.

0022-3565/02/3031-0110$00.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2002 by U.S. Government


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Chen and M. E. Charness
Ethanol inhibits neuronal differentiation by disrupting activity-dependent neuroprotective protein signaling
PNAS, December 16, 2008; 105(50): 19962 - 19967.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
R. A. Harris, J. R. Trudell, and S. J. Mihic
Ethanol's Molecular Targets
Sci. Signal., July 15, 2008; 1(28): re7 - re7.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. Arevalo, S. Shanmugasundararaj, M. F. Wilkemeyer, X. Dou, S. Chen, M. E. Charness, and K. W. Miller
An alcohol binding site on the neural cell adhesion molecule L1
PNAS, January 8, 2008; 105(1): 371 - 375.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
C. R. Goodlett, K. H. Horn, and F. C. Zhou
Alcohol Teratogenesis: Mechanisms of Damage and Strategies for Intervention
Experimental Biology and Medicine, June 1, 2005; 230(6): 394 - 406.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
L. Qin, M. L. Block, Y. Liu, R. J. Bienstock, Z. Pei, W. Zhang, X. Wu, B. Wilson, T. Burka, and J.-S. Hong
Microglial NADPH oxidase is a novel target for femtomolar neuroprotection against oxidative stress
FASEB J, April 1, 2005; 19(6): 550 - 557.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. F. Wilkemeyer, S.-y. Chen, C. E. Menkari, K. K. Sulik, and M. E. Charness
Ethanol Antagonist Peptides: Structural Specificity without Stereospecificity
J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 1183 - 1189.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. E. Brenneman, C. Y. Spong, J. M. Hauser, D. Abebe, A. Pinhasov, T. Golian, and I. Gozes
Protective Peptides That Are Orally Active and Mechanistically Nonchiral
J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 1190 - 1197.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. A. Greenberg
Linking acquired neurodevelopmental disorders to defects in cell adhesion
PNAS, July 8, 2003; 100(14): 8043 - 8044.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. F. Wilkemeyer, S.-y. Chen, C. E. Menkari, D. E. Brenneman, K. K. Sulik, and M. E. Charness
Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity
PNAS, July 8, 2003; 100(14): 8543 - 8548.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics.