PXD007714

PXD007714 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomic analysis in brain of fathead minnows exposed to ethinyl estradiol and levonorgestrel
Description	Adverse outcome pathways (AOPs) are conceptual frameworks that organize and link contaminant-induced molecular changes to adverse biological responses at the individual and population level. The development of AOPs is a priority area of research in ecotoxicology as a means to leverage molecular and high content mechanistic information obtained through top-down ‘omic approaches in regulatory decision-making. Current AOPs for hormonally active agents (HAAs) focus on nuclear receptor-mediated effects despite the overwhelming evidence that HAAs also activate membrane receptors. Activation of membrane receptors triggers propagation of non-genomic signaling cascades often transduced by protein phosphorylation leading to phenotypic changes. To promote investigations of rapid non-genomic signaling mechanisms of environmental contaminants in aquatic species for top-down AOP development, we developed a phosphoproteomic pipeline using label-free LC-MS/MS. We used our optimized pipeline to identify proteins differentially phosphorylated in the brain of fathead minnows (Pimephales promelas) aqueously exposed for 30 minutes to two HAAs, 17α-ethinylestradiol (EE2), a strong estrogenic substance, and levonorgestrel (LNG), a progestin, both components of the birth control pill. Results revealed differential phosphorylation of proteins involved in neuronal processes such as nervous system development, synaptic transmission, and neuroprotection by EE2 while LNG induced differential phosphorylation of proteins involved in axon cargo transport and calcium ion homeostasis. EE2 and LNG caused similar enrichment of cell processes including synaptic plasticity and neurogenesis. This study is the first to identify molecular changes in vivo in fish after short-term exposure and highlights membrane receptors and transduction of rapid, non-genomic signaling mechanisms as targets of HAAs in addition to the well-established nuclear receptor-mediated pathways.
HostingRepository	PRIDE
AnnounceDate	2018-07-11
AnnouncementXML	Submission_2018-07-11_07:01:50.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ley Smith
SpeciesList	scientific name: Pimephales promelas; NCBI TaxID: 90988;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	LTQ Orbitrap; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-11 03:50:18	ID requested
⏵ 1	2018-07-11 07:01:52	announced

Smith LC, Lavelle CM, Silva-Sanchez C, Denslow ND, Sabo-Attwood T, Early phosphoproteomic changes for adverse outcome pathway development in the fathead minnow (Pimephales promelas) brain. Sci Rep, 8(1):10212(2018) [pubmed]

curator keyword: Biological

submitter keyword: fathead minnow QE Plus LTQ Orbitrap phosphopeptide toxicology

Tara Sabo-Attwood
contact affiliation	Department of Environmental and Global Health, College of Public Health and Health Profession, University of Florida, Gainesville, FL
contact email	sabo@phhp.ufl.edu
lab head
Ley Smith
contact affiliation	University of Florida
contact email	leycodysmith@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007714
     1. Label: PRIDE project
     2. Name: Phosphoproteomic analysis in brain of fathead minnows exposed to ethinyl estradiol and levonorgestrel