Editor's Highlight: Glutathione S-Transferase Activity Moderates Methylmercury Toxicity During Development in Drosophila Article Swipe
Daria Vorojeikina
,
Karin Bröberg
,
Tanzy Love
,
Philip W. Davidson
,
Edwin van Wijngaarden
,
Matthew D. Rand
·
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1093/toxsci/kfx033
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1093/toxsci/kfx033
Glutathione (GSH) pathways play a central role in methylmercury (MeHg) metabolism and elimination, largely due to formation of a more readily transported MeHg-GSH conjugate. Glutathione S-transferases (GSTs) have therefore been proposed to facilitate MeHg elimination by catalyzing MeHg-GSH conjugation. A role for human GSTP1 in MeHg disposition is suggested by the association of two common polymorphisms in the coding region (Ile105Val and Ala114Val) with Hg levels in either blood or hair. In this study, we investigated a functional role for GSTs in modulating MeHg toxicity during development. Using the Drosophila model to execute targeted manipulations of both endogenous GSTs and introduced human GSTP1 variants we correlate gene and protein expression levels with GST activity and also with MeHg body burden and developmental outcomes. RNAi knockdown of endogenous GSTD1, GSTE1, or GSTS1, individually, increased susceptibility to MeHg during pupal development resulting in a reduced rate of adult eclosion. Exogenous expression of human GSTP1 in developing flies resulted in increased MeHg tolerance relative to control flies as seen with elevated eclosion rates when reared on MeHg containing food. Furthermore, the GSTP1105 and GSTP1114 variants showed a reduced enzyme activity relative to wild-type GSTP1 (GSTP1wt). Finally, we observed a trend whereby Hg body burden was inversely related to the levels of GST activity. However, in some instances GSTP1 expression resulted in increased eclosion rates without reducing Hg body burden suggesting that GSTs interact with MeHg via both toxicokinetic and toxicodynamic mechanisms. These findings indicate that GSTs moderate MeHg toxicity during development in our experimental model.
Related Topics
Concepts
GSTP1
Glutathione
Toxicity
Methylmercury
Glutathione S-transferase
Chemistry
Gene knockdown
Endogeny
Biochemistry
Enzyme
Toxicology
Biology
Gene
Environmental chemistry
Bioaccumulation
Organic chemistry
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/toxsci/kfx033
- https://academic.oup.com/toxsci/article-pdf/157/1/211/24194909/kfx033.pdf
- OA Status
- bronze
- Cited By
- 35
- References
- 43
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2809968701
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2809968701Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/toxsci/kfx033Digital Object Identifier
- Title
-
Editor's Highlight: Glutathione S-Transferase Activity Moderates Methylmercury Toxicity During Development in DrosophilaWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2017Year of publication
- Publication date
-
2017-02-10Full publication date if available
- Authors
-
Daria Vorojeikina, Karin Bröberg, Tanzy Love, Philip W. Davidson, Edwin van Wijngaarden, Matthew D. RandList of authors in order
- Landing page
-
https://doi.org/10.1093/toxsci/kfx033Publisher landing page
- PDF URL
-
https://academic.oup.com/toxsci/article-pdf/157/1/211/24194909/kfx033.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
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https://academic.oup.com/toxsci/article-pdf/157/1/211/24194909/kfx033.pdfDirect OA link when available
- Concepts
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GSTP1, Glutathione, Toxicity, Methylmercury, Glutathione S-transferase, Chemistry, Gene knockdown, Endogeny, Biochemistry, Enzyme, Toxicology, Biology, Gene, Environmental chemistry, Bioaccumulation, Organic chemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
35Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 3, 2023: 7, 2022: 2, 2021: 4Per-year citation counts (last 5 years)
- References (count)
-
43Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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