Crude oil exposures reveal roles for intracellular calcium cycling in haddock craniofacial and cardiac development.

Elin Sørhus,Rolf B Edvardsen,John P Incardona,Trond Nordtug,Sissel Jentoft,Terje Van Der Meeren,Sonnich Meier,Ørjan Karlsen,Tiffany Linbo,Lisbet Sørensen,Anders Thorsen,Maja Thorbjørnsen

doi:10.1038/srep31058

Abstract

Recent studies have shown that crude oil exposure affects cardiac development in fish by disrupting excitation-contraction (EC) coupling. We previously found that eggs of Atlantic haddock (Melanogrammus aeglefinus) bind dispersed oil droplets, potentially leading to more profound toxic effects from uptake of polycyclic aromatic hydrocarbons (PAHs). Using lower concentrations of dispersed crude oil (0.7–7 μg/L ∑PAH), here we exposed a broader range of developmental stages over both short and prolonged durations. We quantified effects on cardiac function and morphogenesis, characterized novel craniofacial defects, and examined the expression of genes encoding potential targets underlying cardiac and craniofacial defects. Because of oil droplet binding, a 24-hr exposure was sufficient to create severe cardiac and craniofacial abnormalities. The specific nature of the craniofacial abnormalities suggests that crude oil may target common craniofacial and cardiac precursor cells either directly or indirectly by affecting ion channels and intracellular calcium in particular. Furthermore, down-regulation of genes encoding specific components of the EC coupling machinery suggests that crude oil disrupts excitation-transcription coupling or normal feedback regulation of ion channels blocked by PAHs. These data support a unifying hypothesis whereby depletion of intracellular calcium pools by crude oil-derived PAHs disrupts several pathways critical for organogenesis in fish.

Highlights

Decades indicate that tricyclic subclasses of PAHs disrupt cardiac function, leading to developmental defects in the hearts of exposed embryos[11,13,14]
Both of these effects were observed in isolated fish cardiomyocytes following crude oil exposure in a manner that was dependent on the concentration of tricyclic PAHs24
Crude oil exposure leads to blockade of both Erg channels and intracellular Ca2+ cycling mediated by ryanodine receptor (RyR) or Serca[224], providing an aryl hydrocarbon receptor (AhR)-independent mechanism explaining the whole heart effects observed in exposed embryos

Summary

Introduction

Decades indicate that tricyclic subclasses of PAHs disrupt cardiac function, leading to developmental defects in the hearts of exposed embryos[11,13,14]. Studies encompassing crude oils from several sources, individual PAHs, and multiple fish species indicate a common cardiotoxic response in exposed embryos that includes defects in contractility and heart rate and rhythm[13,14,20,21,22,24,25,26,27]. Compounds that block Erg (e.g., terfenadine) prolong action potentials, leading to reduced heart rate (bradycardia) and arrhythmia[30], while disruption of Ca2+ cycling leads to reduced contractility[36] Both of these effects were observed in isolated fish cardiomyocytes following crude oil exposure in a manner that was dependent on the concentration of tricyclic PAHs24. The visible injury phenotype was compared to the expression of genes encoding potential molecular targets of PAHs in EC coupling to further characterize potential mechanisms of crude oil cardiotoxicity and novel craniofacial abnormalities

Methods

Results

Discussion

Conclusion