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A systems biology approach reveals a calcium-dependent mechanism for basal toxicity in Daphnia magna
Antczak, Philip White, Thomas A. Giri, Anirudha Michelangeli, Francesco Viant, Mark R. Cronin, Mark T. D. Vulpe, Chris Falciani, Francesco
Antczak, Philip
White, Thomas A.
Giri, Anirudha
Michelangeli, Francesco
Viant, Mark R.
Cronin, Mark T. D.
Vulpe, Chris
Falciani, Francesco
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2015-08-05
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Abstract
The expanding diversity and ever increasing amounts of man-made chemicals discharged to the environment pose largely unknown hazards to ecosystem and human health. The concept of adverse outcome pathways (AOPs) emerged as a comprehensive framework for risk assessment. However, the limited mechanistic information available for most chemicals and a lack of biological pathway annotation in many species represent significant challenges to effective implementation of this approach. Here, a systems level, multistep modeling strategy demonstrates how to integrate information on chemical structure with mechanistic insight from genomic studies, and phenotypic effects to define a putative adverse outcome pathway. Results indicated that transcriptional changes indicative of intracellular calcium mobilization were significantly overrepresented in Daphnia magna (DM) exposed to sublethal doses of presumed narcotic chemicals with log Kow ≥ 1.8. Treatment of DM with a calcium ATPase pump inhibitor substantially recapitulated the common transcriptional changes. We hypothesize that calcium mobilization is a potential key molecular initiating event in DM basal (narcosis) toxicity. Heart beat rate analysis and metabolome analysis indicated sublethal effects consistent with perturbations of calcium preceding overt acute toxicity. Together, the results indicate that altered calcium homeostasis may be a key early event in basal toxicity or narcosis induced by lipophilic compounds.
Citation
Antczak, P., White, T. A., Giri, A., Michelangeli, F., Viant, M. R., Cronin, M. T. D., Vulpe, C., & Falciani, F. (2015). A systems biology approach reveals a calcium-dependent mechanism for basal toxicity in daphnia magna. Environmental Science & Technology, 49(18), 11132-40. https://doi.org/10.1021/acs.est.5b02707
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American Chemical Society
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Environmental Science & Technology
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Article
Language
en
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This document is the Accepted Manuscript version of a Published Work that appeared in final form in Environmental Science & Technology, copyright © American Chemical Society after peer review and technical editing by the publisher.
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0013-936X
EISSN
1520-5851