Regulation of Heme Uptake and Transport in Caco-2 Cells

该提案的总体目标包括一项计划，以促进Aliye Ue博士的职业发展， 肠血红素摄取和运输的研究。Uc博士的长期职业目标是发展 研究技能和经验，成为一个独立的临床科学家，能够使有意义的 对生物医学科学的贡献。这一奖项将使她能够实现她的直接目标，促进她的 通过课程学习，了解血红素-肠上皮细胞在分子水平上的相互作用， 细胞和分子生物学研究技能。这一奖项将使Uc博士能够继续她的调查， 海涅与肠上皮细胞的相互作用、对电解质转运的影响以及氧化应激的可能作用 强调调节这一功能。这个职业发展计划将发生在爱荷华州，一个理想的大学 Uc博士作为一名临床科学家的发展环境，与布拉德利E。布里蒂根担任她的主要 导师和约翰B博士。斯托克斯担任共同导师。这种环境将为Uc博士提供资源和充分的 获得关键的专业知识，需要在她的研究兴趣领域做出重大贡献。拟议 一项研究项目调查了血红素吸收和跨细胞转运的细胞机制， 良好建立的肠上皮细胞模型，Caco-2细胞。海涅提供了身体的大部分铁，但很少 知道它通过肠道吸收。据推测，海涅是收购和运输在这两个 方向（顶端到基底外侧，反之亦然）的肠上皮细胞通过一个积极的过程，也是 参与电解质运输。这一概念将通过追求以下具体目标来检验： 确定肠上皮细胞血红素摄取的机制以及HO-1、细胞内血红素和 铁水平在调节这一过程中的作用; 2）确定跨细胞肠上皮细胞 血红素转运以及HO-1、细胞内海涅和铁水平在调节这一过程中的作用;以及3）确定 与转运伯尔尼有关的电解质转运蛋白。这些研究将提供新的见解， 了解海涅在正常和疾病状态下通过肠道的运输（例如遗传性血色病，铁 超负荷继发于输血），并探讨肠上皮细胞双向血红素的作用 关于规范铁库存的运动。

The overall goal of this proposal includes a plan to foster the career development of Dr. Aliye Ue while undertaking the investigation of intestinal heme uptake and transport through the intestines. Dr. Uc's long term career goal is to develop the research skills and experience to become an independent clinician scientist, capable of making meaningful contribution to biomedical sciences. This award would allow her to fulfill her immediate goals for furthering her understanding of heme-intestinal epithelial cell interactions at a molecular level through course work and attaining new research skills in cellular and molecular biology. This award would enable Dr. Uc to continue her investigation on the interactions of heine with the intestinal epithelium, its effect on electrolyte transport and possible role of oxidative stress in modulating this function. This career development plan would take place at the University of Iowa, an ideal environment for Dr. Uc's development as a clinical scientist, with Dr. Bradley E. Britigan serving as her primary mentor and Dr. John B. Stokes acting as co-mentor. This environment will provide Dr. Uc both resources and full access to critical expertise, needed to make significant contribution in the area of her research interest. The proposed research project investigates the cellular mechanisms involved in absorption and transcellular transport of heme in a well-established intestinal epithelial cell model, Caco-2 ceils. Heine provides the majority of body's iron, but little is known about its absorption through the intestines. It is hypothesized that heine is acquired and transported in both directions (apical to basolateral and vice versa) by the intestinal epithelial cells via an active process that is also involved in electrolyte transport. This concept will be tested by the pursuit of the following specific aims: 1) Determine the mechanisms involved in intestinal epithelial heme uptake and the role of HO-1, intracellular heme and iron levels in regulating this process; 2) Determine the mechanisms involved in transcellular intestinal epithelial cell heme transport and the role of HO-1, intracellular heine and iron levels in regulating this process; and 3) Determine the electrolyte transporter(s) associated with the transport of berne. These studies will provide new insight into understanding heine transport through intestines in normal and disease states (e.g. hereditary hemochromatosis, iron overload secondary to blood transfusions) and explore the role of intestinal epithelial cell bi-directional heme movement on the regulation of iron stores.