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Alcohol and Alcoholism Advance Access originally published online on March 31, 2006
Alcohol and Alcoholism 2006 41(3):300-305; doi:10.1093/alcalc/agl021
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© The Author 2006. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved

APO-AII IS AN ELEVATED BIOMARKER OF CHRONIC NON-HUMAN PRIMATE ETHANOL SELF-ADMINISTRATION

WILLARD M. FREEMAN1,*, RANDY S. GOOCH2, MELINDA E. LULL1, TRAVIS J. WORST2, STEPHEN J. WALKER2, ARRON S. L. XU3, HEATHER GREEN2, PETER J. PIERRE2, KATHLEEN A. GRANT2 and KENT E. VRANA1

1 Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA, 2 Department of Physiology and Pharmacology, Wake Forest University, Winston-Salem, NC, USA and 3 Ciphergen Biosystems, Inc., Fremont, CA, USA

* Author to whom correspondence should be addressed at: Department of Pharmacology, H078, Penn State College of Medicine, 500 University Drive, PO Box 850, Hershey, PA 17033-0850, USA. Tel: +1 717 531 4037 (ext. 280248); Fax: +1 717 531 5013, E-mail: wfreeman{at}psu.edu

(Received 30 September 2005; first review notified 14 December 2005; accepted in revised form 1 March 2006)

Aims: Serum protein profiles were examined in naïve, ethanol self-administering and ethanol abstinent cynomolgus monkeys (Macaca fasicularis) to search for differences in protein expression which could possibly serve as biomarkers of heavy ethanol consumption. Methods: Surface-enhanced laser desorption ionization time-of-flight (SELDI-ToF) mass spectrometry was used for proteomic profiling of serum. Results: Two proteins were identified by SELDI-ToF to be increased in ethanol self-administering compared with abstinent animals. These proteins were identified to be apolipoprotein AI (Apo-AI) and apolipoprotein AII (Apo-AII) by peptide mass fingerprinting and comparison with spectra of purified human Apo-AI and AII proteins. Immunoblot analysis of Apo-AI and Apo-AII was performed on a separate group of animals (within-animal ethanol-naïve and self-administering) and confirmed a statistically significant increase in Apo-AII, while Apo-AI was unchanged. Conclusions: An open proteomic screen of serum and confirmation in a separate set of animals found Apo-AII to be increased in the serum of ethanol self-administering monkeys. These results are consistent with previous clinical studies of human ethanol consumption and serum apolipoprotein expression. Moreover, these results validate the use of non-human primates as a model organism for proteomic analysis of ethanol self-administration biomarkers.


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