Restored iron transport by a small molecule promotes absorption and hemoglobinization in animals

Science
Anthony S GrilloMartin D Burke

Abstract

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.

References

Feb 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·C FriendT Sato
Jun 16, 1995·Biochemical Pharmacology·R J WardR R Crichton
Oct 27, 1999·Gastroenterology·M H MendlerY Deugnier
Dec 23, 1999·The New England Journal of Medicine·N C Andrews
Apr 25, 2000·Annual Review of Medicine·S Sheth, G M Brittenham
Jan 10, 2001·Proceedings of the National Academy of Sciences of the United States of America·B S BerlettE R Stadtman
Feb 24, 2001·Molecular Aspects of Medicine·P T LieuY Yang
Mar 17, 2001·Nature Reviews. Genetics·N C Andrews
Oct 24, 2001·Human Molecular Genetics·C N Roy, N C Andrews
Aug 28, 2002·Biochemical Society Transactions·B P EspósitoZ I Cabantchik
Aug 30, 2002·Applied and Environmental Microbiology·P N DioufE Gelhaye
Feb 8, 2003·Advances in Experimental Medicine and Biology·Joan L BussPrem Ponka
Feb 6, 2004·Blood Cells, Molecules & Diseases·Antonello Pietrangelo
Jan 5, 2005·Toxicology and Applied Pharmacology·G Papanikolaou, K Pantopoulos
Jan 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Mitchell D KnutsonMarianne Wessling-Resnick
Mar 11, 2005·The New England Journal of Medicine·Guenter Weiss, Lawrence T Goodnough
Dec 3, 2005·Science·Eric Gouaux, Roderick Mackinnon
Dec 21, 2005·Basic & Clinical Pharmacology & Toxicology·Keiko MurakamiMasataka Yoshino
Jan 3, 2006·Pharmaceutical Research·Xi-Ping HuangJ J Thiessen
Mar 3, 2006·Nature·George C ShawBarry H Paw
Mar 24, 2006·Nature·Christopher Miller
Nov 2, 2006·The Journal of Toxicological Sciences·Norio ImaiTomoyuki Shirai
Dec 25, 2007·The Journal of Pediatrics·A IolasconC Beaumont
Nov 5, 2008·Journal of Medical Genetics·A GregoryS J Hayflick
Apr 3, 2009·Nature Reviews. Molecular Cell Biology·David C Gadsby
Apr 27, 2010·Biochemical and Biophysical Research Communications·Myong Jin LeeEun Gyeong Yang

❮ Previous
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Citations

Jun 26, 2018·British Journal of Haematology·Clara Camaschella, Alessia Pagani
Aug 5, 2018·Journal of Cellular Biochemistry·Ying ShenPeng Shang
Nov 8, 2018·Blood·Clara Camaschella
Jun 21, 2017·Nature Chemical Biology·Grant Miura
Apr 27, 2018·Nature Reviews. Chemistry·Jonathan W LehmannMartin D Burke
Jul 1, 2017·Nature Reviews. Drug Discovery·Katie Kingwell
Oct 4, 2017·American Journal of Hematology·Immacolata AndolfoAchille Iolascon
Mar 8, 2018·Angewandte Chemie·Melanie Trobe, Martin D Burke
Aug 11, 2019·Pharmaceuticals·Marija Lesjak, Surjit K S Srai
May 24, 2017·Proceedings of the National Academy of Sciences of the United States of America·Andrea M E PalazzoloMartin D Burke
Mar 30, 2018·European Journal of Nutrition·Marija LesjakSurjit Kaila S Srai
Aug 11, 2017·Metallomics : Integrated Biometal Science·Martin D Kafina, Barry H Paw
Mar 19, 2019·Nature·David N Sheppard, Anthony P Davis
Nov 30, 2018·Annual Review of Physiology·Diane M Ward, Suzanne M Cloonan
Aug 2, 2019·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Michael D GarrickAndrew J Ghio
Nov 15, 2019·Nature Communications·Homan KangJonghan Kim
Aug 21, 2020·Learning & Memory·Jack T Rogers, Catherine M Cahill
Oct 22, 2020·Expert Opinion on Investigational Drugs·Vishal M Gohil
Dec 10, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Jithu V JamesMolly Jacob
Feb 18, 2021·Inorganic Chemistry·Quentin GaydonDavid Scott Bohle
Oct 6, 2020·Biochemical and Biophysical Research Communications·Zhiqing WangBing Zhou
Feb 25, 2020·Free Radical Biology & Medicine·Andrew J GhioMichael C Madden
Mar 2, 2021·Journal of the American Chemical Society·Shuaiwei QiZeyuan Dong
Apr 13, 2021·International Journal of Pharmaceutics·Riddhi Trivedi, Kalyani Barve
May 28, 2021·Haematologica·Stephanie PellegrinAshley M Toye
Jun 7, 2021·Trends in Pharmacological Sciences·Karolin RoemhildTwan Lammers
Jun 10, 2021·ACS Chemical Biology·Usama AbbasiJayachandran N Kizhakkedathu
Aug 17, 2021·Dalton Transactions : an International Journal of Inorganic Chemistry·Christopher DeLaneyMarcetta Y Darensbourg
May 23, 2020·Journal of the American Chemical Society·Fang-Fang ShenDan Yang
Jun 30, 2019·Inorganic Chemistry·Elizabeth W Hunsaker, Katherine J Franz
Nov 6, 2018·Journal of the American Chemical Society·Hannah M S HaleyMartin D Burke
Apr 14, 2018·ACS Chemical Biology·Michael J LambrechtRyan A Shenvi
Aug 28, 2021·Frontiers in Cell and Developmental Biology·Jiahui TangYiqing Li
Oct 15, 2021·Biological Trace Element Research·Fredson Torres Silva, Breno Pannia Espósito

❮ Previous
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