Restored iron transport by a small molecule promotes absorption and hemoglobinization in animals
| العنوان: | Restored iron transport by a small molecule promotes absorption and hemoglobinization in animals |
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| المؤلفون: | Jacob B. Anderson, Martin D. Kafina, Barry H. Paw, Young Ah Seo, Kiran Subedi, Bruno G. Nicolau, Marianne Wessling-Resnick, Santamaria Anna, Christopher Nardone, Nicholas C. Huston, Murui Han, Yvette Y. Yien, Alexander G. Cioffi, Archita Venugopal Menon, Jonghan Kim, John D. Hong, Anthony S. Grillo, James Z. Fan, Andrew A. Gewirth, Martin D. Burke, Dillon C. Svoboda |
| المصدر: | Science. 356:608-616 |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Iron, Saccharomyces cerevisiae, Article, Tropolone, Hemoglobins, 03 medical and health sciences, Hinokitiol, chemistry.chemical_compound, Iron-Binding Proteins, Homeostasis, Animals, Humans, Zebrafish, Multidisciplinary, biology, Transporter, DMT1, biology.organism_classification, Small molecule, Transmembrane protein, Rats, 030104 developmental biology, Membrane, chemistry, Biochemistry, Metals, Gastrointestinal Absorption, Monoterpenes, biology.protein, Biophysics, Caco-2 Cells, Flux (metabolism) |
| الوصف: | Multiple human diseases ensue from a hereditary or acquired deficiency of iron-transporting protein function that diminishes transmembrane iron flux in distinct sites and directions. Because other iron-transport proteins remain active, labile iron gradients build up across the corresponding protein-deficient membranes. Here we report that a small-molecule natural product, hinokitiol, can harness such gradients to restore iron transport into, within, and/or out of cells. The same compound promotes gut iron absorption in DMT1-deficient rats and ferroportin-deficient mice, as well as hemoglobinization in DMT1- and mitoferrin-deficient zebrafish. These findings illuminate a general mechanistic framework for small molecule-mediated site- and direction-selective restoration of iron transport. They also suggest that small molecules that partially mimic the function of missing protein transporters of iron, and possibly other ions, may have potential in treating human diseases. |
| تدمد: | 1095-9203 0036-8075 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a4ad378d8c7997f59df6b6b9d64557eTest https://doi.org/10.1126/science.aah3862Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2a4ad378d8c7997f59df6b6b9d64557e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10959203 00368075 |
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