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

摘要

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.