Glutathione and multidrug resistance protein transporter mediate a self-propelled disposal of bismuth in human cells

Proceedings of the National Academy of Sciences of the United States of America
Yifan HongHongzhe Sun

Abstract

Glutathione and multidrug resistance protein (MRP) play an important role on the metabolism of a variety of drugs. Bismuth drugs have been used to treat gastrointestinal disorder and Helicobacter pylori infection for decades without exerting acute toxicity. They were found to interact with a wide variety of biomolecules, but the major metabolic pathway remains unknown. For the first time (to our knowledge), we systematically and quantitatively studied the metabolism of bismuth in human cells. Our data demonstrated that over 90% of bismuth was passively absorbed, conjugated to glutathione, and transported into vesicles by MRP transporter. Mathematical modeling of the system reveals an interesting phenomenon. Passively absorbed bismuth consumes intracellular glutathione, which therefore activates de novo biosynthesis of glutathione. Reciprocally, sequestration by glutathione facilitates the passive uptake of bismuth and thus completes a self-sustaining positive feedback circle. This mechanism robustly removes bismuth from both intra- and extracellular space, protecting critical systems of human body from acute toxicity. It elucidates the selectivity of bismuth drugs between human and pathogens that lack of glutathione, such as He...Continue Reading

References

Mar 1, 1978·Journal of Bacteriology·R C FaheyM B Worsham
Jun 1, 1977·International Journal of Dermatology·R Degos
Feb 9, 1974·British Medical Journal·R BurnsV J Barron
Sep 1, 1993·Molecular and Biochemical Parasitology·D M BrownP Upcroft
Jun 4, 1999·Trends in Microbiology·B P Rosen
Oct 3, 1999·The Journal of Biological Chemistry·H SunP J Sadler
Oct 19, 2000·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·G DanscherR Pamphlett
Mar 29, 2001·Acta Neuropathologica·M StoltenbergG Danscher
Apr 18, 2001·Archives of Toxicology·B T LeussinkJ A Bruijn
Jun 22, 2002·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·M StoltenbergU T Brunk
Aug 5, 2003·Molecular and Cellular Biology·Arnaud ParcellierCarmen Garrido
Aug 20, 2003·Molecular Biology of the Cell·Asha Rajagopal, Sanford M Simon
Jul 24, 2004·Journal of Inorganic Biochemistry·Lan JinHongzhe Sun
Aug 18, 2004·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Meredin Stoltenberg, James C Hutson
Apr 23, 2005·Toxicology and Applied Pharmacology·Nazzareno BallatoriRosemarie Marchan
Jun 28, 2005·Antimicrobial Agents and Chemotherapy·Toshiaki KotaniTatsuo Yagura
Dec 13, 2005·Biochemistry. Biokhimii︠a︡·G V Smirnova, O N Oktyabrsky
Jul 6, 2006·Trends in Pharmacological Sciences·Susan P C Cole, Roger G Deeley
May 16, 2007·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Ruiguang GeHongzhe Sun
Jul 25, 2007·Angewandte Chemie·Nan YangJian-Dong Huang
Jul 8, 2008·Toxicology Letters·Albanin Aparecida Mielniczki-PereiraJoão Antonio Pêgas Henriques
Jul 22, 2008·Brain Research Bulletin·Li-Hong ZhangZhan-You Wang
Oct 23, 2009·British Journal of Pharmacology·Mauro Perretti, Jesmond Dalli
Aug 1, 1999·Toxicology in Vitro : an International Journal Published in Association with BIBRA·M C Sousa, J Poiares-da-Silva
Jun 7, 2011·Nature Reviews. Gastroenterology & Hepatology·Javier P Gisbert
Dec 27, 2011·Journal of Inorganic Biochemistry·Elaine M Leslie
Feb 11, 2012·Current Opinion in Chemical Biology·Hongyan Li, Hongzhe Sun
Oct 18, 2012·Alimentary Pharmacology & Therapeutics·C Y TayB J Marshall
Nov 28, 2013·Immunology and Cell Biology·Maria PittelliAlberto Chiarugi
Sep 25, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Donal M Keogan, Darren M Griffith

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Citations

Apr 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Isolda Romero-Canelón, Peter J Sadler
Jun 18, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·D M KeoganD M Griffith
Sep 24, 2015·Chemical Communications : Chem Comm·Yuchuan WangHongzhe Sun
Oct 7, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Tasuku HirayamaHideko Nagasawa
Feb 1, 2018·Nature Communications·Runming WangHongzhe Sun
Jun 11, 2019·Metallomics : Integrated Biometal Science·Tianfan ChengLijian Jin
Jan 9, 2020·Chemical Communications : Chem Comm·Siming YuanYangzhong Liu
Apr 28, 2020·Metallomics : Integrated Biometal Science·Stephen A PearsonJ A Cowan
Jan 29, 2021·Organic & Biomolecular Chemistry·Akari MukaimineHideko Nagasawa
Apr 22, 2021·Current Opinion in Chemical Biology·Fabio Arnesano
Mar 27, 2021·Metallomics : Integrated Biometal Science·Stephen A Pearson, J A Cowan
Jun 30, 2021·Cancer Biotherapy & Radiopharmaceuticals·Nouran R R ZaidGerhard Glatting
Jul 13, 2019·Inorganic Chemistry·Yuchuan WangHongzhe Sun
Sep 18, 2021·Chemical Society Reviews·Darren M GriffithHongzhe Sun

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