ZFIN ID: ZDB-PUB-140527-8
Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish
Teraoka, H., Okuno, Y., Nijoukubo, D., Yamakoshi, A., Peterson, R.E., Stegeman, J.J., Kitazawa, T., Hiraga, T., Kubota, A.
Date: 2014
Source: Aquatic toxicology (Amsterdam, Netherlands)   154C: 19-26 (Journal)
Registered Authors: Peterson, Richard E., Stegeman, John J., Teraoka, Hiroki
Keywords: Cyclooxygenase, Danio rerio, Developmental toxicology, Edema, TCDD, Thromboxane
MeSH Terms:
  • Animals
  • Antioxidants/pharmacology
  • Aryl Hydrocarbon Receptor Nuclear Translocator/genetics
  • Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism
  • Ascorbic Acid/pharmacology
  • Cyclooxygenase 2/metabolism*
  • Cyclooxygenase 2 Inhibitors/pharmacology
  • Edema, Cardiac/chemically induced*
  • Edema, Cardiac/enzymology
  • Edema, Cardiac/physiopathology*
  • Embryo, Nonmammalian/drug effects
  • Gene Expression Regulation, Enzymologic/drug effects
  • Gene Knockdown Techniques
  • Receptors, Aryl Hydrocarbon/genetics
  • Receptors, Aryl Hydrocarbon/metabolism
  • Signal Transduction/drug effects
  • Thromboxanes/metabolism*
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish/growth & development*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 24858302 Full text @ Aquat. Toxicol.
The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration-response curve for precardiac edema at 2days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3dpf. These results suggest a role of the COX2b-thromboxane pathway in precardiac edema formation following TCDD exposure in developing zebrafish.