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小鼠硫酸转移酶的组织分布及个体发生

Tissue distribution and ontogeny of sulfotransferase enzymes in mice.

作者信息

Alnouti Yazen, Klaassen Curtis D

机构信息

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.

出版信息

Toxicol Sci. 2006 Oct;93(2):242-55. doi: 10.1093/toxsci/kfl050. Epub 2006 Jun 28.

Abstract

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.

摘要

磺基转移酶(Sults)是Ⅱ相缀合酶,可催化磺酸基团从3'-磷酸腺苷5'-磷酸硫酸酯(PAPS)转移至内源性和外源性靶标。PAPS由无机硫酸盐通过PAPS合酶(PAPSs)的作用形成。在本研究中,对小鼠体内11种Sult同工酶和2种PAPSs同工型的mRNA表达的组织分布及发育变化进行了定量分析。使用分支DNA信号放大测定法对雄性和雌性小鼠14种组织中的Sult1a1、1b1、1c1、1c2、1d1、1e1、2a1/2、2b1、3a1、4a1、5a1、PAPSs1和PAPSs2的mRNA表达进行了定量分析。Sult2a1/2和3a1在肝脏中的表达最高;Sult1b1、2b1和PAPSs2在小肠中表达最高;Sult1a1在大肠中表达最高;Sult1c2在胃中表达最高;Sult1d1在肾脏中表达最高;Sult1e1在胎盘中表达最高;Sult4a1在大脑中表达最高。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约3周龄逐渐增加,此后略有下降;Sult1c1的表达在出生前最高,之后下降;Sult3a1的mRNA表达在胎儿肝脏中非常低,直到30日龄时仍保持低水平,此时雌性小鼠的表达急剧增加,而雄性小鼠的表达从未增加。Sults的器官特异性分布以及幼龄动物中Sults的不同表达可能会影响外源性物质的药代动力学行为和器官特异性毒性。

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