Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Structure-Activity Relationships for Hydroxylated Polychlorinated Biphenyls as Substrates and Inhibitors of Rat Sulfotransferases and Modification of These Relationships by Changes in Thiol Status

Yungang Liu, Jason T. Smart, Yang Song, Hans-Joachim Lehmler, Larry W. Robertson and Michael W. Duffel
Drug Metabolism and Disposition May 2009, 37 (5) 1065-1072; DOI: https://doi.org/10.1124/dmd.108.026021
Yungang Liu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jason T. Smart
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yang Song
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hans-Joachim Lehmler
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Larry W. Robertson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael W. Duffel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) are inhibitors and substrates for various human sulfotransferases (SULTs). Although the rat is often used in toxicological studies on PCBs, the interactions of OH-PCBs with rat SULTs are less well understood. In the present study, 15 OH-PCBs were investigated as potential substrates or inhibitors of purified recombinant rSULT1A1 and rSULT2A3, the major family 1 and family 2 SULTs present in rat liver, respectively. None of these OH-PCBs were substrates for rSULT2A3, 11 weakly inhibited rSULT2A3-catalyzed sulfation of dehydroepiandrosterone, and 4 had no effect on the reaction. With rSULT1A1, 4-OH-PCB 8, 4′-OH-PCB 3, 9, 12, 35, and 6′-OH-PCB 35 were substrates, whereas 4′-OH-PCB 6, 4-OH-PCB 14, 4′-OH-PCB 25, 4′-OH-PCB 33, 4-OH-PCB 34, 4-OH-PCB36, 4′-OH-PCB 36, 4′-OH-PCB 68, and 4-OH-PCB 78 inhibited the sulfation of 2-naphthol catalyzed by this enzyme. OH-PCBs with a 3,5-dichloro-4-hydroxy substitution were the most potent inhibitors of rSULT1A1, and the placement of chlorine atoms in the ortho- and meta-positions on either ring of para-OH-PCBs resulted in significant differences in activity as substrates and inhibitors. The specificity of rSULT1A1 for several inhibitory OH-PCBs was altered by pretreatment of the enzyme with oxidized glutathione (GSSG). Four OH-PCBs that were inhibitors of rSULT1A1 under reducing conditions became substrates after pretreatment of the enzyme with GSSG. This alteration in specificity of rSULT1A1 for certain OH-PCBs suggests that conditions of oxidative stress may significantly alter the sulfation of some OH-PCBs in the rat.

Footnotes

  • This work was supported in part by the National Institutes of Health National Institute of Environmental Health Sciences [Grants P42-ES013661, K25-ES012475, P30-ES05605]; and the National Institutes of Health National Cancer Institute [Grant R01-CA038683]. We also acknowledge programmatic support through the University of Iowa Environmental Health Sciences Research Center.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.108.026021.

  • ABBREVIATIONS: PCB, polychlorinated biphenyl; OH-PCB, hydroxylated polychlorinated biphenyl; SULT, sulfotransferase; h, human; r, rat; DHEA, dehydroepiandrosterone; GC, gas chromatography; MS, mass spectrometry; PAPS, adenosine 3′-phosphate 5′-phosphosulfate; PAP, adenosine 3′,5′-diphosphate; DTT, dithiothreitol; DTNB, 5,5′-dithiobis(2-nitrobenzoic acid); GSH, reduced glutathione; GSSG, oxidized glutathione.

    • Received December 5, 2008.
    • Accepted January 29, 2009.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 37 (5)
Drug Metabolism and Disposition
Vol. 37, Issue 5
1 May 2009
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Structure-Activity Relationships for Hydroxylated Polychlorinated Biphenyls as Substrates and Inhibitors of Rat Sulfotransferases and Modification of These Relationships by Changes in Thiol Status
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Structure-Activity Relationships for Hydroxylated Polychlorinated Biphenyls as Substrates and Inhibitors of Rat Sulfotransferases and Modification of These Relationships by Changes in Thiol Status

Yungang Liu, Jason T. Smart, Yang Song, Hans-Joachim Lehmler, Larry W. Robertson and Michael W. Duffel
Drug Metabolism and Disposition May 1, 2009, 37 (5) 1065-1072; DOI: https://doi.org/10.1124/dmd.108.026021

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Structure-Activity Relationships for Hydroxylated Polychlorinated Biphenyls as Substrates and Inhibitors of Rat Sulfotransferases and Modification of These Relationships by Changes in Thiol Status

Yungang Liu, Jason T. Smart, Yang Song, Hans-Joachim Lehmler, Larry W. Robertson and Michael W. Duffel
Drug Metabolism and Disposition May 1, 2009, 37 (5) 1065-1072; DOI: https://doi.org/10.1124/dmd.108.026021
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Identification of payload-containing catabolites of ADCs
  • PK Interactions of Licorice with Cytochrome P450s
  • Biotransformation of Trastuzumab and Pertuzumab
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics