Hartman Jessica H, Kozal Jordan S, Di Giulio Richard T, Meyer Joel N
Nicholas School of the Environment, Duke University, Durham, NC, United States.
Nicholas School of the Environment, Duke University, Durham, NC, United States.
Environ Toxicol Pharmacol. 2017 Sep;54:142-145. doi: 10.1016/j.etap.2017.07.004. Epub 2017 Jul 10.
Zebrafish are an attractive model organism for toxicology; however, an important consideration in translating between species is xenobiotic metabolism/bioactivation. CYP2E1 metabolizes small hydrophobic molecules, e.g. ethanol, cigarette smoke, and diesel exhaust components. CYP2E1 is thought to only be conserved in mammals, but recent reports identified homologous zebrafish cytochrome P450s. Herein, ex vivo biochemical measurements show that unlike mammals, zebrafish possess a low-affinity 4-nitrophenol hydroxylase (K ∼0.6 mM) in hepatic microsomes and mitochondria that is inducible only 1.5- to 2-fold by ethanol and is insensitive to 4-methylpyrazole inhibition. In closing, we suggest creating improved models to study CYP2E1 in zebrafish.
斑马鱼是毒理学中一种有吸引力的模式生物;然而,在不同物种间进行转化时,一个重要的考虑因素是外源性物质的代谢/生物活化。CYP2E1代谢小的疏水分子,例如乙醇、香烟烟雾和柴油废气成分。CYP2E1被认为仅在哺乳动物中保守,但最近的报告鉴定出了斑马鱼细胞色素P450的同源物。在此,体外生化测量表明,与哺乳动物不同,斑马鱼在肝微粒体和线粒体中具有低亲和力的4-硝基苯酚羟化酶(K~0.6 mM),该酶仅被乙醇诱导1.5至2倍,且对4-甲基吡唑抑制不敏感。最后,我们建议创建改进的模型来研究斑马鱼中的CYP2E1。