BLT-1, a specific inhibitor of the HDL receptor SR-BI, induces a copper-dependent phenotype during zebrafish development.
Block lipid transport-1 (BLT-1) is a small chemical widely used to inhibit the transfer of lipids between high-density lipoproteins (HDL) and cells mediated by scavenger receptor B, type 1 (SR-BI). This study demonstrated that BLT-1 induced in zebrafish (Danio rerio) embryos a copper-dependent phenotype with a twisted notochord, brain ventricle enlargement, and absence of melanisation, phenocopying neocuproine-treated, or calamity mutants. This finding supports an unexpected link between copper availability and SR-BI activity. The copper-chelating activity of BLT-1, revealed by its dramatic effect during embryo development, should be considered in any evaluation of the pharmacological effect of this thiosemicarbazone derivative on SR-BI activity and the potential therapeutic value of this molecule.
Raldúa
Demetrio
D
Laboratory of Environmental Toxicology (UPC), CN150, 08220 Terrassa, Spain.
Babin
Patrick J
PJ
D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000187:drug effects; D002614:Chelating Agents / Q000633:toxicity*; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D003517:Cyclopentanes / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects*; D008543:Melanins / Q000378:metabolism; D009672:Notochord / Q000002:abnormalities / Q000187:drug effects; D010641:Phenotype; D020011:Protective Agents / Q000494:pharmacology; D051122:Scavenger Receptors, Class B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012880:Skin Pigmentation / Q000187:drug effects; D013882:Thiosemicarbazones / Q000633:toxicity*; D015027:Zebrafish / Q000002:abnormalities*
C526651:2-hexyl-1-cyclopentanone thiosemicarbazone; D002614:Chelating Agents; D003517:Cyclopentanes; D008543:Melanins; D020011:Protective Agents; D051122:Scavenger Receptors, Class B; D013882:Thiosemicarbazones; D003300:Copper; C029892:cupric chloride