Selenium-responsive proteins in the sera of selenium-enriched yeast-supplemented healthy African American and Caucasian men.
Selenium-responsive proteins in the sera of selenium-enriched yeast-supplemented healthy African American and Caucasian men.
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DOI：
10.1158/1055-9965.epi-10-0253
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发表时间：
2010-09
期刊：
影响因子：
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通讯作者：
El-Bayoumy K
中科院分区：
文献类型：
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作者：
Sinha R;Sinha I;Facompre N;Russell S;Somiari RI;Richie JP Jr;El-Bayoumy K
研究表明，给成年男性补充富硒酵母（SY）对前列腺癌（PCa）有预防作用，还能降低氧化应激和前列腺特异抗原（PSA）水平。在此，我们确定了补充SY对健康男性血清总蛋白表达的影响，以便为硒化学预防机制提供新的见解；这些蛋白质也可作为疾病进展的生物标志物。
从我们之前的SY临床试验中获取了36名成年男性的血清样本，这些样本是在补充SY（247μg/d）（n = 17）或安慰剂（非富硒酵母）（n = 19）9个月后采集的。
采用二维差异凝胶电泳（2D - DIGE）结合液相色谱 - 串联质谱（LC/MS/MS）进行蛋白质组学分析，共发现1496种候选蛋白质，其中与安慰剂组相比，SY组中有11种蛋白质表达存在差异。8种蛋白质上调（簇集素异构体1[CLU]、转甲状腺素蛋白、α - 1B - 糖蛋白、转铁蛋白、补体成分4B前体蛋白、异柠檬酸脱氢酶、触珠蛋白、角蛋白1），3种蛋白质下调（α - 1抗胰蛋白酶[AAT]、血管紧张素前体和白蛋白前体）。所有已鉴定的蛋白质对氧化还原敏感或参与氧化还原状态的调节。由于AAT和CLU先前都与前列腺癌的发展有关，通过二维蛋白质印迹分析对它们进行了确认。
我们确定AAT和CLU是参与SY预防前列腺癌机制的潜在候选蛋白质。总体而言，本研究中鉴定的蛋白质可作为潜在的新型生物标志物，用于监测和比较对基于硒的化学预防剂的反应。
血清蛋白质组学分析可能有助于化学预防剂的早期检测和疗效监测。
Studies demonstrated that supplementation of adult men with selenium-enriched yeast (SY) was protective against prostate cancer (PCa) and also reduced oxidative stress and levels of PSA. Here we determined the effect of SY supplementation on global serum protein expression in healthy men to provide new insights into the mechanism of selenium chemoprevention; such proteins may also serve as biomarkers of disease progression. Serum samples from 36 adult men were obtained from our previous SY clinical trial, 9 months after supplementation with either SY (247 μg/d) (n=17) or placebo (non-enriched yeast) (n=19). Proteomic profiling using 2D-DIGE followed by LC/MS/MS revealed a total of 1496 candidate proteins, of which, 11 were differentially expressed in the SY group as compared to placebo. Eight proteins were up-regulated (clusterin isoform 1 [CLU], transthyretin, α-1B-glycoprotein, transferrin, complement component 4B proprotein, isocitrate dehydrogenase, haptoglobin, keratin 1) and 3 proteins were down-regulated (α-1 antitrypsin [AAT], angiotensin precursor and albumin precursor) by SY. All of the identified proteins were redox-sensitive or involved in regulation of redox status. Since both ATT and CLU have been previously linked to PCa development, their identities were confirmed by 2D Western blot analysis. We identified AAT and CLU as potential candidate proteins involved in the mechanism of PCa prevention by SY. Collectively, proteins identified in this study may serve as potential new biomarkers for monitoring and comparing responses to selenium-based chemopreventive agents. Proteomic analysis of serum may be useful for early detection and monitoring efficacy of chemopreventive agents.