Intestinal exposure to metals: impact on cell differentiation and intestinal cell funtions.

肠道接触金属：对细胞分化和肠道细胞功能的影响。

• 批准号: 203202-2011
• 负责人: Jumarie, Catherine
• 金额: $ 1.75万
• 依托单位: Université du Québec à Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=523391
• 关键词: Intestinal; exposure; metals; impact; cell

Cadmium (Cd), for which Canada ranks in the top five producers, has various industrial uses. In humans, the two main routes of absorption are inhalation (occupational exposure and smokers) and ingestion through contaminated food products (general population). During decades we have studied the intestinal uptake of Cd as a function of metal speciation (i.e. chemical metal species) focusing on inhibition by essential metals. During the past five years we began to study the intestinal epithelium as a target tissue following metal ingestion. This epithelium is subjected to rapid and constant renewal for which cellular proliferation and maturation are temporally- and functionally-linked phenomena for which some cellular protein play crucial role. We have recently shown that Cd may modify the activity of some of these intracellular proteins which regulate the intestinal cell maturation. We have also observed that the intestinal cell may develop some resistance to Cd but the capacity to acquire this resistance vary considerably with the cell maturation status. Finally, we have shown that there are excretory pathways for Cd in intestinal cells that are also expected to vary with the cell maturation status. We thus plan to pursue our investigation on how Cd may impact on the cell maturation processes and the intestinal functions, and determine whether the acquired resistance to Cd is reversible. Moreover, because the intestinal epithelium play a critical role in the metabolism of toxic compounds as well as pharmaceutical drugs, we aim better understanding to which extent Cd may modify, by direct or indirect action, this function. The expected results will increase our knowledge on: (1) mechanisms of metal toxicity at the cellular level and; (2) how 'chronic' exposure to low levels of metals affect intestinal metabolism activities which is of great interest for toxicology and pharmacology.

加拿大位列镉 (Cd) 生产国前五位，具有多种工业用途。在人类中，两种主要的吸收途径是吸入（职业接触和吸烟者）和通过受污染的食品摄入（一般人群）。几十年来，我们研究了肠道对镉的吸收与金属形态（即化学金属形态）的函数关系，重点关注必需金属的抑制作用。在过去的五年中，我们开始研究肠上皮作为金属摄入后的靶组织。这种上皮经历快速和持续的更新，其中细胞增殖和成熟是时间和功能上相关的现象，其中一些细胞蛋白起着至关重要的作用。我们最近表明，镉可能会改变一些调节肠细胞成熟的细胞内蛋白质的活性。我们还观察到，肠道细胞可能会对镉产生一定的抵抗力，但获得这种抵抗力的能力随细胞成熟状态的不同而有很大差异。最后，我们发现肠道细胞中镉的排泄途径预计也会随着细胞成熟状态的变化而变化。因此，我们计划继续研究镉如何影响细胞成熟过程和肠道功能，并确定对镉的获得性抵抗是否是可逆的。此外，由于肠上皮在有毒化合物和药物的代谢中发挥着关键作用，我们的目标是更好地了解镉可以通过直接或间接作用在多大程度上改变这种功能。预期结果将增加我们对以下方面的了解：（1）细胞水平的金属毒性机制； (2)“长期”接触低水平的金属如何影响肠道代谢活动，这对于毒理学和药理学来说非常有趣。