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Tracing biodistribution of essential and toxic elements in rat liver through PIXE
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms ( IF 1.4 ) Pub Date : 2020-01-08 , DOI: 10.1016/j.nimb.2019.11.037
Rajbinder K. Virk , M. Shafique , Kalyan Vaid , Shivcharan Verma , Mohinder P. Bansal , Mohan L. Garg , Biraja P. Mohanty

Elements like Ca, Co, Cu, Fe, Mg, Mn, Mo, and Zn are essential to life. Within a living organism, these elements are either present as a free pool or are bound to some biomolecules. Multielemental analysis of biological samples such as tissues, bio-fluids and purified proteins has been useful in the diagnosis of acute/chronic exposure to elements that are foreign to the body. These xenobiotics may induce toxicity either by generation of reactive oxygen species or may displace a native element from its binding site rendering the protein/peptide inactive. In order to explore this proposition, herein, centrifugal filters of varying molecular weight cut-off were used in conjunction with Particle Induced X-ray Emission (PIXE) to quantitatively map the distribution of elements in different molecular weight fractions, segregated from the post mitochondrial fraction (PMF) isolated from the liver tissue of control and arsenic supplemented animals (rats). In addition to this, the whole liver tissue of control and arsenic supplemented animals were also analysed by PIXE. In the liver tissue of rats, treated with chronic human equivalent dose of As, the concentration of As was found to be 6 ppm, whereas, it was below detection limit (<1 ppm) in control animals. Our results also confirm that out of the soluble proteome of the post mitochondrial tissue extract, arsenic is sequestered by the proteins having molecular weight of ≥ 50 kDa. In the protein molecular weight fraction of 10–50 kDa, the concentrations of S, Ca and Mn were increased in case of arsenic treated group as compared to control, whereas, in fractions of ≥ 50 kDa, and 3–10 kDa the levels of these elements were decreased. This procedure proves to be beneficial in tracking biological binding site of a xenobiotic which may further assist in the elucidation of its metabolic pathway and drug design.



中文翻译:

通过PIXE追踪大鼠肝脏中必需和有毒元素的生物分布

诸如Ca,Co,Cu,Fe,Mg,Mn,Mo和Zn等元素对生命至关重要。在生物体内,这些元素要么以自由池的形式存在,要么与某些生物分子结合。对生物样品(例如组织,生物流体和纯化的蛋白质)进行多元素分析已用于诊断对人体异物的急性/慢性暴露。这些异生物可能通过产生活性氧而诱导毒性,或者可能从其结合位点取代天然成分,从而使蛋白质/肽失去活性。为了探索这一命题,在本文中,将不同分子量截断值的离心过滤器与粒子诱导X射线发射(PIXE)结合使用,以定量绘制不同分子量部分中元素的分布,与从对照组和补充砷的动物(大鼠)的肝组织中分离出的线粒体后部分(PMF)分离。除此之外,还通过PIXE分析了对照组和补充砷的动物的整个肝脏组织。在大鼠的肝脏组织中,用慢性人类当量剂量的As处理后,As的浓度为6 ppm,而在对照动物中,As的浓度低于检测极限(<1 ppm)。我们的结果还证实,在线粒体后组织提取物的可溶性蛋白质组中,砷被分子量≥50 kDa的蛋白质螯合。在10–50 kDa的蛋白质分子量分数中,与对照组相比,砷处理组的S,Ca和Mn浓度增加,而在≥50 kDa的分数中,和3–10 kDa时,这些元素的水平降低了。事实证明,该方法在追踪异种生物的生物结合位点方面是有益的,这可以进一步帮助阐明其代谢途径和药物设计。

更新日期:2020-01-08
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