Statistically Enhanced Spectral Counting Approach
to TCDD Cardiac Toxicity in the Adult Zebrafish Heart
- Publication date
- Publisher
Abstract
2,3,7,8-Tetrachlorodibenzo-<i>p</i>-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-dependent variation in
shotgun proteomic experiments and obtain a statistically significant
protein data set 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 ratios above 2 and 43 proteins
displayed NSAF ratios smaller than 0.5, with statistical significance
by <i>t</i> test (<i>p</i> < 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