Proteomic approaches for studying alcoholism and alcohol-induced organ damage.
Bottom Line: These studies have identified proteins in various brain regions whose expression is affected by alcohol.Other investigators have used proteomic approaches to identify proteins that could serve as potential biomarkers of alcohol use.Finally, interaction proteomic analyses have begun to identify proteins involved in several nerve signaling networks in the brain, which then can serve as targets for further studies on alcohol's effects.
Affiliation: CSR, Incorporated, Arlington, Virginia.
Proteomics research is concerned with the analysis of all proteins found in an organism, tissue, cell type, or cellular structure. The shotgun proteomic approach, which involves two-dimensional gel electrophoresis or liquid chromatography combined with mass spectrometry (MS), is used to identify novel proteins affected by alcohol. More targeted analyses study protein-protein interactions using such techniques as the yeast two-hybrid system, affinity chromatography, or immunoprecipitation. Finally, proteomic strategies can be combined with genomic research findings using computer analyses (i.e., in silico). All of these approaches have been used in the alcohol field. These studies have identified proteins in various brain regions whose expression is affected by alcohol. Other investigators have used proteomic approaches to identify proteins that could serve as potential biomarkers of alcohol use. Finally, interaction proteomic analyses have begun to identify proteins involved in several nerve signaling networks in the brain, which then can serve as targets for further studies on alcohol's effects. Future proteomic studies likely will shed more light on the mechanisms underlying alcohol's actions on the body.
Related in: MedlinePlus
Mentions: Chronic alcohol exposure leads to a wide range of changes in brain function. On the one hand, alcohol damages neurons in various brain regions, leading to cognitive impairment and other abnormalities in brain function in alcoholics. On the other hand, the brain adapts to the constant presence of alcohol, trying to counteract alcohol’s harmful effects. (This adaptation leads to withdrawal symptoms if alcohol levels suddenly drop.) Both alcohol’s damaging effect on the brain and the body’s adaptive response may be mediated, at least in part, by altered protein expression. To evaluate this assumption, Lewohl and colleagues (2004) studied the proteome of one brain region affected by alcohol—the superior frontal cortex (SFC)—of long-term alcoholics and healthy control subjects, using autopsy samples. Using 2-DE, the investigators compared proteins from the healthy and alcoholic subjects for differential expression (i.e., differences in abundance of a given protein of two-fold or more between the two groups). This analysis detected 182 proteins with differential expression, including 139 proteins that were less abundant in alcoholics, 35 proteins that were more abundant in alcoholics, and 8 proteins that were found only in alcoholics or nonalcoholics (see figure 4). However, these analyses did not yet provide any information on the nature and function of these proteins. By subsequently using MALDI-MS and tandem MS, the investigators were able to identify 63 of the 182 proteins; these fell into several groups based on their physiological functions. The researchers concluded that proteomic studies can be conducted on autopsy samples to identify candidate proteins that are affected by long-term alcohol use and whose exact roles can be analyzed further.