PMID- 22692990 OWN - NLM STAT- MEDLINE DCOM- 20121029 LR - 20120704 IS - 1439-7633 (Electronic) IS - 1439-4227 (Linking) VI - 13 IP - 10 DP - 2012 Jul 9 TI - Cardiosulfa induces heart deformation in zebrafish through the AhR-mediated, CYP1A-independent pathway. PG - 1483-9 LID - 10.1002/cbic.201200177 [doi] AB - 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. CI - Copyright (c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Ko, Sung-Kyun AU - Ko SK AD - Center for Biofunctional Molecules, Department of Chemistry, Yonsei University, 120-749 Seoul, Korea. FAU - Shin, Injae AU - Shin I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120612 PL - Germany TA - Chembiochem JT - Chembiochem : a European journal of chemical biology JID - 100937360 RN - 0 (2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide) RN - 0 (Azo Compounds) RN - 0 (Carbazoles) RN - 0 (Pyrazoles) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors, Aryl Hydrocarbon) RN - 0 (Sulfonamides) RN - 0 (Zebrafish Proteins) RN - 0 (cardiosulfa) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1A1) SB - IM MH - Animals MH - Azo Compounds/chemistry/pharmacology MH - Carbazoles/chemistry/*pharmacology MH - Cytochrome P-450 CYP1A1/metabolism MH - Embryo, Nonmammalian/drug effects/metabolism MH - Gene Expression Regulation, Developmental MH - Heart/*drug effects MH - Hep G2 Cells MH - Humans MH - Pyrazoles/chemistry/pharmacology MH - RNA Interference MH - RNA, Small Interfering/metabolism MH - Receptors, Aryl Hydrocarbon/antagonists & inhibitors/genetics/*metabolism MH - Signal Transduction MH - Sulfonamides/chemistry/*pharmacology MH - Transfection MH - Zebrafish/metabolism MH - Zebrafish Proteins/antagonists & inhibitors/*metabolism EDAT- 2012/06/14 06:00 MHDA- 2012/10/30 06:00 CRDT- 2012/06/14 06:00 PHST- 2012/03/13 00:00 [received] PHST- 2012/06/14 06:00 [entrez] PHST- 2012/06/14 06:00 [pubmed] PHST- 2012/10/30 06:00 [medline] AID - 10.1002/cbic.201200177 [doi] PST - ppublish SO - Chembiochem. 2012 Jul 9;13(10):1483-9. doi: 10.1002/cbic.201200177. Epub 2012 Jun 12.