Cardiosulfa induces heart deformation in zebrafish through the AhR-mediated, CYP1A-independent pathway.
Heart development is a complicated and elaborate biological process. To study this and similar complicated process and diseases, the discovery and use of small molecules for probing biological events is invaluable. As part of such an investigation, we have identified cardiosulfa, a small molecule that induces severely impaired heart morphology and function in zebrafish. The results of the present study show that cardiosulfa-promoted heart deformation is protected by negative regulators of the aryl hydrocarbon receptor (AhR) signaling pathway, such as the AhR antagonist CH-223191 and an AhR2-morpholino antisense oligonucleotide, zfahr2-MO. However, the toxic effect of cardiosulfa is not alleviated by zfcyp1a-MO, a morpholino antisense oligo for cytochrome P450 1A (CYP1A), which is the most well-characterized gene of the AhR pathway. Similar results were obtained for the known AhR agonist PCB126. These observations suggest that cardiosulfa causes heart deformation in zebrafish through the AhR-mediated, CYP1A-independent pathway. Our results indicate that cardiosulfa has potential as a novel type of a biological probe to investigate the AhR pathway.
Center for Biofunctional Molecules, Department of Chemistry, Yonsei University, 120-749 Seoul, Korea.
Sung-Kyun
SK
Ko
Injae
I
Shin
D000818:Animals; D001391:Azo Compounds / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D014162:Transfection; D015027:Zebrafish / Q000378:metabolism; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
C511621:2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide; D001391:Azo Compounds; D002227:Carbazoles; D011720:Pyrazoles; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon; D013449:Sulfonamides; D029961:Zebrafish Proteins; C545674:cardiosulfa; D019363:Cytochrome P-450 CYP1A1