Division of Epidemiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK.
Proteomics. 2011 May;11(10):1903-14. doi: 10.1002/pmic.201000580. Epub 2011 Apr 4.
The mycotoxin deoxynivalenol (DON) contaminates cereals worldwide and is a common contaminant in the Western European diet. At high doses, DON induces acute gastrointestinal toxicity; chronic, low-dose effects in humans are not well described, but immunotoxicity has been reported. In this study, 2-DE was used to identify proteomic changes in human B (RPMI1788) and T (JurkatE6.1) lymphocyte cell lines after exposure to minimally toxic concentrations (up to 500 ng/mL) for 24 h. Proteins which changed their abundance post treatment, by a greater than 1.4-fold change reproducible in three separate experiments consisting of 36 gels in total, are ubiquitin carboxyl-terminal hydrolase isozyme L3, proteasome subunit β type-4 and α type-6, inosine-5'-monophosphate dehydrogenase 2, GMP synthase, microtubule-associated protein RP/EB family member 1 (EB1), RNA polymerases I, II, III subunit ABC1, triosephosphate isomerase and transketolase. Flow cytometry was used to validate changes to protein expression, except for EB1. These findings provide insights as to how low-dose exposure to DON may affect human immune function and may provide mechanism-based biomarkers for DON exposure.
真菌毒素脱氧雪腐镰刀菌烯醇(DON)污染了世界各地的谷物,是西欧饮食中的一种常见污染物。在高剂量下,DON 会引起急性胃肠道毒性;人类慢性、低剂量的影响尚未得到很好描述,但已有免疫毒性的报道。在这项研究中,2-DE 被用于鉴定人类 B(RPMI1788)和 T(JurkatE6.1)淋巴细胞系在暴露于最小毒性浓度(高达 500ng/mL)24 小时后的蛋白质组学变化。在总共 36 张凝胶的三个独立实验中,处理后丰度变化超过 1.4 倍且可重复的蛋白质有泛素羧基末端水解酶同工酶 L3、蛋白酶体亚基β类型-4 和α类型-6、肌苷 5'-单磷酸脱氢酶 2、GMP 合酶、微管相关蛋白 RP/EB 家族成员 1(EB1)、RNA 聚合酶 I、II、III 亚基 ABC1、磷酸丙糖异构酶和转酮醇酶。流式细胞术用于验证蛋白质表达的变化,但不包括 EB1。这些发现提供了关于低剂量 DON 暴露如何影响人类免疫功能的见解,并可能为 DON 暴露提供基于机制的生物标志物。