Analysis of protein expression in developmental toxicity induced by MeHg in zebrafish

Abstract

Mercury toxicity and its implications in development are a major concern, due to the major threat to ecosystems and human health that this compound represents. Although some of the effects of methylmercury (MeHg) exposure have been extensively studied, the molecular mechanisms of interaction between this compound and developing organisms are still not completely understood. To provide further insights into these mechanisms, we carried out a quantitative proteomic study (iTRAQ) using zebrafish larvae exposed to 5 μg L(-1) and 25 μg L(-1) MeHg as a model. In this study, a multidimensional approach combining isoelectric focusing (IEF) and strong cation exchange (SCX) followed by reversed phase liquid chromatography prior to MALDI TOF/TOF analysis was employed, which resulted in a substantial increase in proteome coverage. Among the proteins identified, 71 were found de-regulated by more than 1.5-fold, and implicated in embryonic development, protein synthesis, calcium homeostasis and energy production. Furthermore, morphological and histological analysis of exposed larvae was carried out, reflecting changes such as smaller swim bladder, remaining yolk, bent body axis and accumulation of blood in the heart, among others.

Toxicogenomic Responses of Zebrafish Embryos/Larvae to Tris(1,3-dichloro-2-propyl) Phosphate (TDCPP) Reveal Possible Molecular Mechanisms of Developmental Toxicity

“…Protein expressions were considered statistically significant if the P-value <0.05 and exhibited a fold change >1.50 for up-regulation and <0.70 for down-regulation as described elsewhere. 15,17 Statistical Analyses. The statistical analyses were conducted by use of Kyplot Demo 3.0 software (Tokyo, Japan).…”

Fold-change threshold screening: a robust algorithm to unmask hidden gene expression patterns in noisy aggregated transcriptome data

“…Upregulation of keratin 18 (krt18) in the presence of methylmercury is found in several microarray studies (Nøstbakken et al 2012;Cuello et al 2012). In D. rerio krt18, a member of type I keratin genes, is strongly linked to the development and regeneration of scales as well as the dorsal fin (Padhi et al 2004;Wang et al 2006).…”

Developmental toxicity from exposure to various forms of mercury compounds in medaka fish (Oryzias latipes) embryos

“…Numerous aquatic organisms have been studied with respect to the toxicity of mercury; however, most studies were focused on organic mercury (e.g., MeHg) (Liao et al, 2007; Cuello et al, 2012) and/or inorganic HgCl 2 (Ismail & Yusof, 2011; Wang et al, 2011; Wang et al, 2013). The toxic potential of α -HgS and β -HgS used in traditional medicines is largely unknown.…”

“…Exposures of ≤80 ppm (mg L −1 ) to medaka embryos have increased mortality and caused teratogenic effects including stunted growth, decreased heart rate, and small eyes with reduced pigmentation, among others (Heisinger & Green, 1975; Dial, 1978). In zebrafish ( Danio rerio ) larvae exposed to ≤25 mg L −1 , down-regulation of >70 proteins was associated with morphological changes including but not limited to: smaller swim bladder, unabsorbed yolk, jaw deformities, and bent body axis (Cuello et al, 2012). In the present study, 0.1 µM MeHg produced pericardial edema that in severe cases formed a tube heart, reduced eye pigmentation, and failed swim bladder inflation.…”