PUBLICATION

Statistically Enhanced Spectral Counting Approach to TCDD Cardiac Toxicity in the Adult Zebrafish Heart

Authors
Zhang, J., Lanham, K.A., Heideman, W., Peterson, R.E., and Li, L.
ID
ZDB-PUB-130611-21
Date
2013
Source
Journal of Proteome Research   12(7): 3093-103 (Journal)
Registered Authors
Heideman, Warren, Peterson, Richard E.
Keywords
none
MeSH Terms
  • Animals
  • Embryo, Nonmammalian
  • Environmental Pollutants/toxicity
  • Heart/drug effects
  • Heart/growth & development*
  • Proteins/isolation & purification*
  • Proteomics
  • Zebrafish/growth & development*
PubMed
23682714 Full text @ J. Proteome Res.
Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant and teratogen that produces cardiac toxicity in the developing zebrafish. Here we adopted a label free quantitative proteomic approach based on normalized spectral abundance factor (NSAF) to investigate the disturbance of the cardiac proteome induced by TCDD in the adult zebrafish heart. The protein expression level changes between heart samples from TCDD treated and control zebrafish were systematically evaluated by a large scale MudPIT analysis which incorporated triplicate analyses for both control and TCDD exposed heart proteomic samples to overcome the data dependant variation in shotgun proteomic experiments and obtain a statistically significant protein dataset with improved quantification confidence. A total of 519 and 443 proteins were identified in hearts collected from control and TCDD treated zebrafish, respectively, among which 106 proteins showed statistically significant expression changes. After correcting for the experimental variation between replicate analyses by statistical evaluation, 55 proteins exhibited NSAF ratio above 2 and 43 proteins displayed NSAF ratio smaller than 0.5, with statistical significance by t-test (p < 0.05). The proteins identified as altered by TCDD encompass a wide range of biological functions including calcium handling, myocardium cell architecture, energy production and metabolism, mitochondrial homeostasis, and stress response. Collectively, our results indicate that TCDD exposure alters the adult zebrafish heart in a way that could result in cardiac hypertrophy and heart failure, and suggests a potential mechanism for the diastolic dysfunction observed in TCDD exposed embryos.

Genes / Markers
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes