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

TitleGlutathione and multidrug resistance protein transporter mediate a self-propelled disposal of bismuth in human cells
Authors
Issue Date2015
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences, 2015, v. 112, p. 3211-3216 How to Cite?
AbstractGlutathione 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 Helicobacter pylori, opening new horizons for further drug development.
Persistent Identifierhttp://hdl.handle.net/10722/211712
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHONG, Y-
dc.contributor.authorLAI, YT-
dc.contributor.authorChan, GCF-
dc.contributor.authorSun, H-
dc.date.accessioned2015-07-21T02:08:41Z-
dc.date.available2015-07-21T02:08:41Z-
dc.date.issued2015-
dc.identifier.citationProceedings of the National Academy of Sciences, 2015, v. 112, p. 3211-3216-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/211712-
dc.description.abstractGlutathione 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 Helicobacter pylori, opening new horizons for further drug development.-
dc.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.titleGlutathione and multidrug resistance protein transporter mediate a self-propelled disposal of bismuth in human cells-
dc.typeArticle-
dc.identifier.emailChan, GCF: gcfchan@hku.hk-
dc.identifier.emailSun, H: hsun@hku.hk-
dc.identifier.authorityChan, GCF=rp00431-
dc.identifier.authoritySun, H=rp00777-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1421002112-
dc.identifier.pmid25737551-
dc.identifier.pmcidPMC4371909-
dc.identifier.scopuseid_2-s2.0-84925258882-
dc.identifier.hkuros245255-
dc.identifier.volume112-
dc.identifier.spage3211-
dc.identifier.epage3216-
dc.identifier.isiWOS:000351060000040-
dc.publisher.placeUnited States-

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