Tissue distribution and ontogeny of sulfotransferase enzymes in mice
Tissue distribution and ontogeny of sulfotransferase enzymes in mice
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DOI：
10.1093/toxsci/kfl050
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发表时间：
2006-10-01
影响因子：
3.8
通讯作者：
Klaassen, Curtis D.
中科院分区：
文献类型：
--
作者：
Alnouti, Yazen;Klaassen, Curtis D.
磺基转移酶是一种第二相结合酶，催化磺酸基从3‘-磷酸腺苷-5’-磷酸转移到靶向内源和外源化合物。PAPS是由无机硫酸盐在PPS合成酶(PAPSS)的作用下形成的。本研究定量研究了11种SULT同工酶和2种PAPSS亚型在小鼠体内的组织分布和发育变化。用分支DNA信号扩增法检测了雄性和雌性小鼠14个组织中Sult1a1、1b1、1c1、1c2、1d1、1e1、2a1/2、2b1、3a1、4a1、5a1、PAPSs1和PAPSs2mRNA的表达。Sult2a1/2和3a1在肝脏中表达最高，在小肠中表达最高，在大肠中表达最高，在胃中表达最高，在肾脏中表达最高，在胎盘中表达最高，在脑中表达最高。Sult1c1、5a1和PAPSs1在大多数组织中普遍表达。这些酶在肝脏中表现出三种不同的个体发育表达模式。Sult1a1、1c2、1d1、2a1/2和PAPSs2的肝脏表达从出生到3周左右逐渐增加，之后有所下降，Sult1c1在出生前表达最高，之后下降；Sult3a1在胎肝中的表达很低，直到30日龄，雌性表达显著增加，而雄性表达一直没有增加。硫磺在幼年动物体内的器官特异性分布以及表达的不同可能影响外源化合物的药代动力学行为和器官特异性毒性。
Sulfotransferases (Sults) are phase-II conjugation enzymes that catalyze the transfer of a sulfonate group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to target endo and xenobiotics. PAPS is formed from inorganic sulfate by the action of the enzyme PAPS synthase (PAPSs). In the present study, the tissue distribution and developmental changes in the mRNA expression of 11 Sult isozymes and 2 PAPSs isoforms in mice were quantified. Sult1a1, 1b1, 1c1, 1c2, 1d1, 1e1, 2a1/2, 2b1, 3a1, 4a1, 5a1, PAPSs1, and PAPSs2 mRNA expression was quantified in 14 tissues from male and female mice using the branched DNA signal amplification assay. Sult2a1/2 and 3a1 expression were highest in liver; Sult1b1, 2b1, and PAPSs2 in small intestine; Sult1a1 in large intestine; Sult1c2 in stomach; Sult1d1 in kidney; Sult1e1 in placenta; and Sult4a1 in brain. Sult1c1, 5a1, and PAPSs1 were ubiquitously expressed in most tissues. These enzymes demonstrated three different ontogenic expression patterns in liver. Sult1a1, 1c2, 1d1, 2a1/2, and PAPSs2 hepatic expression gradually increased from birth until about 3 weeks of age and then declined somewhat thereafter, Sult1c1 expression was highest before birth and declined after that, and Sult3a1 mRNA expression was very low in fetal livers and remained low until 30 days of age, when expression in females dramatically increased, whereas it never increased in males. The organ-specific distribution of Sults as well as the different expression of the Sults in young animals may affect the pharmacokinetic behavior and organ-specific toxicity of xenobiotics.