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  • Sethi, SunjayDepartment of Molecular Biosciences, University of California - Davis, Davis, USA (author)

Comparative Analyses of the 12 Most Abundant PCB Congeners Detected in Human Maternal Serum for Activity at the Thyroid Hormone Receptor and Ryanodine Receptor

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-03-01
  • American Chemical Society (ACS),2019
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:oru-83806
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-83806URI
  • https://doi.org/10.1021/acs.est.9b00535DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agency:National Institutes of Health (NIH) - USA, Grant Number: R01 ES014901, R01 ES030318, P30 ES023513, P01 ES011269, T32 ES007059United States Environmental Protection Agency, Grant Number: RD 83543201Superfund Research Center at The University of Iowa, Grant Number: P42 ES013661
  • Polychlorinated biphenyls (PCBs) pose significant risk to the developing human brain; however, mechanisms of PCB developmental neurotoxicity (DNT) remain controversial. Two widely posited mechanisms are tested here using PCBs identified in pregnant women in the MARBLES cohort who are at increased risk for having a child with a neurodevelopmental disorder (NDD). As determined by gas chromatography-triple quadruple mass spectrometry, the mean PCB level in maternal serum was 2.22 ng/mL. The 12 most abundant PCBs were tested singly and as a mixture mimicking the congener profile in maternal serum for activity at the thyroid hormone receptor (THR) and ryanodine receptor (RyR). Neither the mixture nor the individual congeners (2 fM to 2 μM) exhibited agonistic or antagonistic activity in a THR reporter cell line. However, as determined by equilibrium binding of [3H]ryanodine to RyR1-enriched microsomes, the mixture and the individual congeners (50 nM to 50 μM) increased RyR activity by 2.4-19.2-fold. 4-Hydroxy (OH) and 4-sulfate metabolites of PCBs 11 and 52 had no TH activity; but 4-OH PCB 52 had higher potency than the parent congener toward RyR. These data support evidence implicating RyRs as targets in environmentally triggered NDDs and suggest that PCB effects on the THR are not a predominant mechanism driving PCB DNT. These findings provide scientific rationale regarding a point of departure for quantitative risk assessment of PCB DNT, and identify in vitro assays for screening other environmental pollutants for DNT potential.

Subject headings and genre

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  • Morgan, Rhianna K.Department of Molecular Biosciences, University of California - Davis, Davis, USA (author)
  • Peng, WeiDepartment of Molecular Biosciences, University of California - Davis, Davis, USA (author)
  • Lin, YanpingDepartment of Molecular Biosciences, University of California - Davis, Davis, USA (author)
  • Li, XueshuDepartment of Occupational and Environmental Health, University of Iowa, Iowa City, USA (author)
  • Luna, CoreyDepartment of Molecular Biosciences, University of California - Davis, Davis, USA (author)
  • Koch, MadisonDepartment of Molecular Biosciences, University of California - Davis, Davis, USA (author)
  • Bansal, RubyDepartment of Biology, University of Massachusetts, Amherst, USA (author)
  • Duffel, Michael W.Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa City, USA (author)
  • Puschner, BirgitDepartment of Molecular Biosciences, University of California - Davis, Davis, USA (author)
  • Zoeller, R. Thomas,1952-Department of Biology, University of Massachusetts, Amherst, USA(Swepub:oru)tzr (author)
  • Lehmler, Hans-JoachimDepartment of Occupational and Environmental Health, University of Iowa, Iowa City, USA (author)
  • Pessah, Isaac N.Department of Molecular Biosciences, University of California - Davis, Davis, USA (author)
  • Lein, Pamela J.Department of Molecular Biosciences, University of California - Davis, Davis, USA (author)
  • Department of Molecular Biosciences, University of California - Davis, Davis, USADepartment of Occupational and Environmental Health, University of Iowa, Iowa City, USA (creator_code:org_t)

Related titles

  • In:Environmental Science and Technology: American Chemical Society (ACS)53:7, s. 3948-39580013-936X1520-5851

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