A Systems Biology Approach Reveals a Calcium-Dependent Mechanism for Basal Toxicity in Daphnia magna.

Hdl Handle:
http://hdl.handle.net/10034/607105
Title:
A Systems Biology Approach Reveals a Calcium-Dependent Mechanism for Basal Toxicity in Daphnia magna.
Authors:
Antczak, Philip; White, Thomas A.; Giri, Anirudha; Michelangeli, Francesco; Viant, Mark R.; Cronin, Mark T. D.; Vulpe, Chris; Falciani, Francesco
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.
Affiliation:
University of Birmingham, University of Liverpool, University of California, Berkley, Liverpool John Moores, Assam University
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.
Publisher:
ACS publications
Journal:
Environmental Science & Technology
Publication Date:
1-Sep-2015
URI:
http://hdl.handle.net/10034/607105
DOI:
10.1021/acs.est.5b02707
Additional Links:
http://pubs.acs.org/journal/esthag
Type:
Article
Language:
en
Description:
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.
ISSN:
0013-936X
EISSN:
1520-5851
Appears in Collections:
Biological Sciences

Full metadata record

DC FieldValue Language
dc.contributor.authorAntczak, Philipen
dc.contributor.authorWhite, Thomas A.en
dc.contributor.authorGiri, Anirudhaen
dc.contributor.authorMichelangeli, Francescoen
dc.contributor.authorViant, Mark R.en
dc.contributor.authorCronin, Mark T. D.en
dc.contributor.authorVulpe, Chrisen
dc.contributor.authorFalciani, Francescoen
dc.date.accessioned2016-04-26T11:04:52Zen
dc.date.available2016-04-26T11:04:52Zen
dc.date.issued2015-09-01en
dc.identifier.citationAntczak, 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.en
dc.identifier.issn0013-936Xen
dc.identifier.doi10.1021/acs.est.5b02707en
dc.identifier.urihttp://hdl.handle.net/10034/607105en
dc.descriptionThis 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.en
dc.description.abstractThe 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.en
dc.language.isoenen
dc.publisherACS publicationsen
dc.relation.urlhttp://pubs.acs.org/journal/esthagen
dc.subjecttoxicologyen
dc.subjectsystems biologyen
dc.titleA Systems Biology Approach Reveals a Calcium-Dependent Mechanism for Basal Toxicity in Daphnia magna.en
dc.typeArticleen
dc.identifier.eissn1520-5851en
dc.contributor.departmentUniversity of Birmingham, University of Liverpool, University of California, Berkley, Liverpool John Moores, Assam Universityen
dc.identifier.journalEnvironmental Science & Technologyen
dc.date.accepted2015-08-05en
or.grant.openaccessYesen
rioxxterms.funderunfundeden
rioxxterms.identifier.projectunfunded researchen
rioxxterms.versionAMen
rioxxterms.licenseref.startdate2017-09-01en
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