Asset Details
Do you wish to reserve the book?
Glutathione and multidrug resistance protein transporter mediate a self-propelled disposal of bismuth in human cells
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Glutathione and multidrug resistance protein transporter mediate a self-propelled disposal of bismuth in human cells
Do you wish to request the book?
Glutathione and multidrug resistance protein transporter mediate a self-propelled disposal of bismuth in human cells
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Glutathione and multidrug resistance protein transporter mediate a self-propelled disposal of bismuth in human cells
2015
Overview
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 Helicobacter pylori , opening new horizons for further drug development.
Significance Bismuth compounds have long been used in clinic for the treatment of various diseases, in particular, for Helicobacter pylori infection. We reported the mechanism of uptake of bismuth compounds by mammalian cells and bacteria, and demonstrated a passive transport of the metallodrug. We showed that glutathione and multidrug resistance protein transporter mediate a self-propelled disposal of bismuth antiulcer drug. A model was derived to elucidate the uptake of the metallodrug, and which may readily be extended to other drugs or drug candidates. Our work uncovered the secret of low toxicity of bismuth in human and relatively high drug selectivity against “glutathione-poor” pathogens such as H. pylori .
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Bacteria
/ Bismuth
/ Cell Compartmentation - drug effects
/ Cells
/ drugs
/ Escherichia coli - metabolism
/ Humans
/ Inactivation, Metabolic - drug effects
/ Ion Transport - drug effects
/ Multidrug Resistance-Associated Proteins - metabolism
/ Organometallic Compounds - metabolism
/ Organometallic Compounds - pharmacology
/ Toxicity
