Haudenschild Dominik R, Eldridge Angela, Lein Pamela J, Chromy Brett A
Biochem Biophys Res Commun. 2014 Dec 5;455(1-2):84-9. doi: 10.1016/j.bbrc.2014.09.137.
In order to realize the goal of stratified and/or personalized medicine in the clinic, significant advances in the field of biomarker discovery are necessary. Adding to the abundance of nucleic acid biomarkers being characterized, additional protein biomarkers will be needed to satisfy diverse clinical needs. An appropriate source for finding these biomarkers is within blood, as it contains tissue leakage factors as well as additional proteins that reside in blood that can be linked to the presence of disease. Unfortunately, high abundant proteins and complexity of the blood proteome present significant challenges for the discovery of protein biomarkers from blood. Animal models often enable the discovery of biomarkers that can later be translated to humans. Therefore, determining appropriate sample preparation of proteomic samples in rodent models is an important research goal. Here, we examined both mouse and rat blood samples (including both serum and plasma), for appropriate high abundant protein removal techniques for subsequent gel-based proteomic experiments. We assessed four methods of albumin removal: antibody-based affinity chromatography (MARS), Cibacron® Blue-based affinity depletion (SwellGel® Blue Albumin Removal Kit), protein-based affinity depletion (ProteaPrep Albumin Depletion Kit) and TCA/acetone precipitation. Albumin removal was quantified for each method and SDS-PAGE and 2-DE gels were used to quantify the number of protein spots obtained following albumin removal. Our results suggest that while all four approaches can effectively remove high abundant proteins, antibody-based affinity chromatography is superior to the other three methods.
为了在临床上实现分层医学和/或个性化医学的目标,生物标志物发现领域必须取得重大进展。除了大量正在被表征的核酸生物标志物外,还需要更多的蛋白质生物标志物来满足多样化的临床需求。寻找这些生物标志物的合适来源是血液,因为它含有组织渗漏因子以及血液中存在的可与疾病存在相关联的其他蛋白质。不幸的是,血液蛋白质组中高丰度蛋白质和复杂性给从血液中发现蛋白质生物标志物带来了重大挑战。动物模型常常能够发现后来可转化到人类身上的生物标志物。因此,确定啮齿动物模型中蛋白质组学样品的合适样品制备方法是一个重要的研究目标。在这里,我们检测了小鼠和大鼠的血液样品(包括血清和血浆),以寻找用于后续基于凝胶的蛋白质组学实验的合适的高丰度蛋白质去除技术。我们评估了四种去除白蛋白的方法:基于抗体的亲和色谱法(MARS)、基于Cibacron® Blue的亲和去除法(SwellGel® Blue白蛋白去除试剂盒)、基于蛋白质的亲和去除法(ProteaPrep白蛋白去除试剂盒)和三氯乙酸/丙酮沉淀法。对每种方法的白蛋白去除量进行了定量,并使用SDS-PAGE和双向电泳凝胶来定量去除白蛋白后获得的蛋白质斑点数量。我们的结果表明,虽然所有四种方法都能有效去除高丰度蛋白质,但基于抗体的亲和色谱法优于其他三种方法。