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.

加拿大在前五名生产商中排名的镉（CD）具有各种工业用途。在人类中，两种主要吸收途径是吸入（职业暴露和吸烟者）和通过污染的食品（一般人群）摄入。在几十年中，我们研究了CD的肠道摄取是金属物种形成（即化学金属物种）的函数，该核心重点是必需金属的抑制作用。在过去的五年中，我们开始研究金属摄入后肠上皮作为靶组织。该上皮受到快速且恒定的更新，对于细胞增殖和成熟是时间和功能连接的现象，某些细胞蛋白起着至关重要的作用。我们最近表明，CD可以改变调节肠细胞成熟的细胞内蛋白的活性。我们还观察到，肠细胞可能会产生对CD的耐药性，但是获得这种抗药性的能力随细胞成熟状态差异很大。最后，我们已经表明，在肠道细胞中，CD的排泄途径也有望随细胞成熟状态而变化。因此，我们计划对CD如何影响细胞成熟过程和肠功能进行调查，并确定获得的CD抗性是否可逆。此外，由于肠上皮在有毒化合物的代谢以及药物中起关键作用，因此我们旨在更好地理解CD可以通过直接或间接作用（该功能）修改该功能的程度。预期的结果将增加我们对：（1）在细胞水平上的金属毒性机制； （2）“慢性”暴露于低水平的金属中如何影响肠道新陈代谢活性，这对毒理学和药理学引起了极大的兴趣。