Proteomics, the study of proteins, may be able to help identify and treat alcohol’s effects on the body

"Proteomics" refers to the study of proteins that are synthesized by cells, tissues and organs in the body. Recent advances in technology now allow scientists to separate and identify these proteins. According to symposium proceedings published in the February issue of Alcoholism: Clinical & Experimental Research, proteomics has important implications for alcoholism research in terms of identifying biomarkers of alcohol intake, understanding alcohol’s effects, particularly on the liver, and developing drugs to treat alcoholism.

"The study of proteins involved in alcoholism has taken two different approaches," said Chinnaswamy Kasinathan, associate professor at the University of Medicine and Dentistry of New Jersey and symposium organizer. "One approach is to select a protein for study because of its role in a pathway believed to involve alcoholism. Since alcoholism is a behavioral disorder, many of the candidate proteins selected for study are involved in neurochemical pathways. An alternate proteomic approach is to study as many proteins as can be separated by a technique such as 2D gel electrophoresis and identified through mass spectrometry. This approach does not select any candidate protein in advance, rather, this approach incorporates and examines the entire proteosome of the body."

The symposium took place at the June 2003 Research Society on Alcoholism meeting in Fort Lauderdale, Florida. Some of the key points were:

- Research designed to identify a urinary biomarker for alcohol intake has found the presence of two groups of proteins in the urine of alcohol-treated rats but not in the urine of control animals.

"The ultimate goal of this research is to apply the animal findings to the development of good urinary biomarkers in humans as a measure of alcohol intake," said Kasinathan.

"This would have important applications for many alcoholism treatment facilities," he added. "For example, there are approximately 17,000 facilities in the United States that treat patients for substance abuse, including alcoholism. The nature of these facilities varies widely, from very small solo practices to very large hospital complexes and residential treatment centers. Many of these facilities do not have easy on-site access to phlebotomists, people who withdraw blood samples for examination. Therefore, urinary tests are more convenient measures of alcohol intake than blood tests in many of these facilities."

- Research using monkeys to identify serum biomarkers of alcohol consumption has found that alcohol consumption significantly elevates levels of a protein called apolipoprotein AII. Results from the same study also suggest that alcohol consumption elevates lipoproteins, which are associated with cardiovascular protective effects.

"These findings contribute further evidence that it is alcohol itself that elicits potential cardiovascular beneficial effects," commented Kent Vrana, the study’s author. "Moreover, this analysis of several hundred proteins, including the identification of two important species, points to the promise of proteomic screening as a tool to better understand the pathophysiological characterization of alcohol abuse and alcoholism."

- Scientists announced a new, international initiative to characterize the liver proteome. It will focus on hepatocellular carcinoma, often associated with cirrhosis, which is commonly cause by alcohol consumption.

Laura Beretta, one of the scientists who will be working with the Human Liver Proteome Project, said its mission would be to characterize and localize proteins in both normal and diseased human liver. "The plan is to involve multiple laboratories internationally," she said, "to build an international network of experts in liver cell biology, proteomics and bioinformatics, and to develop a common bioinformatics platform to track samples with centralized data capture and analysis. The establishment of a ‘liver biological atlas’ would represent a major advance in the understanding of the biological functions of this organ. It may also lead to the development of new therapeutic approaches for liver-specific and other diseases."

Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.

Articles were written based on the following published research:

Kasinathan, C., Vrana, K., Beretta, L., Thomas, P., Gooch, R., Worst, T., Walker, S., Xu, A., Pierre, P., Green, H., Grant, K., & Manowitz, P. (February 2004). The future of proteomics in the study of alcoholism. Alcoholism: Clinical & Experimental Research, 28(2), 228-223.