Protein Biomarker Profiles of Abusive Alcohol Consumption

滥用酒精消费的蛋白质生物标志物概况

• 批准号: 7244096
• 负责人: Frank A Witzmann
• 金额: $ 17.47万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7244096
• 关键词: Protein; Biomarker; Profiles; Abusive; Alcohol

DESCRIPTION (provided by applicant): The long-term objective of this project is to detect a novel biomarker (or confined set of biomarkers) of heavy/abusive alcohol consumption in the plasma of human subjects. The working hypothesis for this aim is that alcohol consumption at high levels elicits cellular and molecular responses whose sequelae are manifest through the appearance of unique and low-abundance polypeptides or proteins in the plasma. These molecules may be derived from a variety of tissues and cells and are unrelated to conventional/traditional markers of alcohol-induced liver injury. We hypothesize that low abundance peptide and low molecular weight protein biomarkers are to be found complexed with high-abundance plasma proteins such as albumin. Our strategy is to preferentially recover these potential biomarkers by plasma albumin affinitycapture, elute and concentrate them, and then acquire whole peptide/protein mass spectra of the mixture. Raw spectral data will then be analyzed, comparing control plasma with samples from alcohol drinkers, and drinkers during early abstinence. Diagnostic peptide/protein patterns will be sought based on various patient classifications. In this regard, our specific aims are to: 1) determine the effect of a defined exposure to alcohol in normal individuals on the plasma proteome, using alcohol clamping to minimize the between-individual variation in alcohol absorption and pharmacokinetics; 2) determine the effect of sustained abusive drinking on the plasma proteome. The subjects will be recruited from patients seeking treatment for alcohol abuse and dependence, and plasma will be sampled at beginning and end of a 6 week intensive outpatient treatment; and 3) determine which proteomic signatures are influenced by patient characteristics such as body mass index, gender, ethnicity, and minor liver test abnormalities.

描述（由申请人提供）：该项目的长期目标是检测人类受试者血浆中重度/滥用酒精消耗的新型生物标志物（或有限的一组生物标志物）。该目标的工作假设是，高水平的饮酒会引起细胞和分子反应，其后遗症通过血浆中独特且低丰度的多肽或蛋白质的出现而显现出来。这些分子可能源自多种组织和细胞，与酒精性肝损伤的常规/传统标记物无关。我们假设低丰度肽和低分子量蛋白质生物标志物被发现与高丰度血浆蛋白（例如白蛋白）复合。我们的策略是通过血浆白蛋白亲和捕获优先回收这些潜在的生物标志物，洗脱并浓缩它们，然后获取混合物的全肽/蛋白质质谱。 然后对原始光谱数据进行分析，将对照血浆与饮酒者和早期戒酒者的样本进行比较。将根据不同的患者分类来寻找诊断肽/蛋白质模式。在这方面，我们的具体目标是：1）确定正常个体中特定的酒精暴露对血浆蛋白质组的影响，使用酒精钳来最大限度地减少酒精吸收和药代动力学的个体间差异； 2) 确定持续酗酒对血浆蛋白质组的影响。受试者将从寻求酒精滥用和酒精依赖治疗的患者中招募，并在为期 6 周的强化门诊治疗开始和结束时采集血浆样本； 3) 确定哪些蛋白质组学特征受患者特征（例如体重指数、性别、种族和轻微肝脏测试异常）的影响。

项目成果

Sample complexity reduction for two-dimensional electrophoresis using solution isoelectric focusing prefractionation.

使用溶液等电聚焦预分级降低二维电泳的样品复杂性。

• DOI: 10.1002/elps.200700707
• 发表时间: 2008
• 期刊: Electrophoresis
• 影响因子: 2.9
• 作者: Richardson,MatthewR;Liu,Sean;Ringham,HeatherN;Chan,Victor;Witzmann,FrankA
• 通讯作者: Witzmann,FrankA

A proteomic workflow for discovery of serum carrier protein-bound biomarker candidates of alcohol abuse using LC-MS/MS.

• DOI: 10.1002/elps.200800775
• 发表时间: 2009-06
• 期刊: ELECTROPHORESIS
• 影响因子: 2.9
• 作者: Lai, Xianyin;Liangpunsakul, Suthat;Crabb, David W.;Ringham, Heather N.;Witzmann, Frank A.
• 通讯作者: Witzmann, Frank A.