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Alcohol and Alcoholism Advance Access published online on March 31, 2006
Alcohol and Alcoholism, 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
Received September 30, 2005
Revised December 14, 2005
Accepted March 1, 2006

Article

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

WILLARD M. FREEMAN 1 *, RANDY S. GOOCH 2, MELINDA E. LULL 1, TRAVIS J. WORST 2, STEPHEN J. WALKER 2, ARRON S. L. XU 3, HEATHER GREEN 2, PETER J. PIERRE 2, KATHLEEN A. GRANT 2, and KENT E. VRANA 1

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
3 Ciphergen Biosystems, Inc., Fremont, CA, USA

* To whom correspondence should be addressed.
WILLARD M. FREEMAN, E-mail: wfreeman{at}psu.edu


  Abstract

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.

The first two authors contributed equally to the work.
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