Suppr超能文献

人肝中胞质磺基转移酶的发育性表达。

Developmental Expression of the Cytosolic Sulfotransferases in Human Liver.

机构信息

Department of Pharmacology (S.D.) and Institute of Environmental Health Sciences (J.A.C., T.A.K., M.R.-M.), Wayne State University, Detroit, Michigan; Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children's Mercy Kansas City, Kansas City, Missouri (R.G., C.A.V.); Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina, Chapel Hill, North Carolina (P.C.S.); and Office of Research and Development, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina (R.N.H.).

Department of Pharmacology (S.D.) and Institute of Environmental Health Sciences (J.A.C., T.A.K., M.R.-M.), Wayne State University, Detroit, Michigan; Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children's Mercy Kansas City, Kansas City, Missouri (R.G., C.A.V.); Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina, Chapel Hill, North Carolina (P.C.S.); and Office of Research and Development, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina (R.N.H.)

出版信息

Drug Metab Dispos. 2019 Jun;47(6):592-600. doi: 10.1124/dmd.119.086363. Epub 2019 Mar 18.

Abstract

The liver is the predominant organ of metabolism for many endogenous and foreign chemicals. Cytosolic sulfotransferases (SULTs) catalyze the sulfonation of drugs and other xenobiotics, as well as hormones, neurotransmitters, and sterols, with consequences that include enhanced drug elimination, hormone inactivation, and procarcinogen bioactivation. SULTs are classified into six gene families, but only SULT1 and SULT2 enzymes are expressed in human liver. We characterized the developmental expression patterns of SULT1 and SULT2 mRNAs and proteins in human liver samples using reverse transcription quantitative polymerase chain reaction (RT-qPCR), RNA sequencing, and targeted quantitative proteomics. Using a set of prenatal, infant, and adult liver specimens, RT-qPCR analysis demonstrated that () expression did not vary appreciably during development; , , and mRNA levels were highest in prenatal and/or infant liver, and , , and mRNA levels were highest in infant and/or adult. Hepatic (), , and mRNA levels were low regardless of developmental stage. Results obtained with RNA sequencing of a different set of liver specimens (prenatal and pediatric) were generally comparable results to those of the RT-qPCR analysis, with the additional finding that expression was highest during gestation. Analysis of SULT protein content in a library of human liver cytosols demonstrated that protein levels generally corresponded to the mRNAs, with the major exception that SULT1C4 protein levels were much lower than expected based on mRNA levels. These findings further support the concept that hepatic SULTs play important metabolic roles throughout the human life course, including early development.

摘要

肝脏是许多内源性和外源性化学物质代谢的主要器官。细胞溶质磺基转移酶(SULTs)催化药物和其他外源性化学物质以及激素、神经递质和甾体的磺化,其后果包括增强药物消除、激素失活和前致癌物的生物激活。SULTs 分为六个基因家族,但只有 SULT1 和 SULT2 酶在人肝中表达。我们使用逆转录定量聚合酶链反应(RT-qPCR)、RNA 测序和靶向定量蛋白质组学,研究了 SULT1 和 SULT2 mRNA 和蛋白质在人肝组织中的发育表达模式。使用一组产前、婴儿和成人肝标本,RT-qPCR 分析表明,()表达在发育过程中没有明显变化;、、和 mRNA 水平在产前和/或婴儿肝中最高,、、和 mRNA 水平在婴儿和/或成人肝中最高。肝()、、和 mRNA 水平无论发育阶段如何均较低。用另一组肝标本(产前和儿科)进行 RNA 测序获得的结果与 RT-qPCR 分析的结果基本一致,另外还发现表达在妊娠期间最高。人肝胞质体 SULT 蛋白含量分析表明,蛋白水平通常与 mRNA 相对应,主要例外是 SULT1C4 蛋白水平远低于基于 mRNA 水平的预期。这些发现进一步支持了这样一种概念,即肝 SULTs 在人类整个生命周期中都发挥着重要的代谢作用,包括早期发育。

相似文献

1
Developmental Expression of the Cytosolic Sulfotransferases in Human Liver.
Drug Metab Dispos. 2019 Jun;47(6):592-600. doi: 10.1124/dmd.119.086363. Epub 2019 Mar 18.
3
Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development.
Drug Metab Dispos. 2018 Aug;46(8):1146-1156. doi: 10.1124/dmd.118.081398. Epub 2018 Jun 1.
4
5
Regulation of sulfotransferase mRNA expression in male and female rats of various ages.
Chem Biol Interact. 1998 Feb 20;109(1-3):299-313. doi: 10.1016/s0009-2797(97)00141-5.
6
Expression of functional sulfotransferases (SULT) 1A1, 1A3, 1B1, 1C2, 1E1, and 2A1 in common marmosets.
Biochem Pharmacol. 2020 Oct;180:114189. doi: 10.1016/j.bcp.2020.114189. Epub 2020 Aug 5.
7
Structure, function and polymorphism of human cytosolic sulfotransferases.
Curr Drug Metab. 2008 Feb;9(2):99-105. doi: 10.2174/138920008783571819.
8
Molecular and functional characterization of cytosolic sulfotransferases in cynomolgus macaque.
Biochem Pharmacol. 2019 Aug;166:153-162. doi: 10.1016/j.bcp.2019.05.018. Epub 2019 May 14.
10
Tissue distribution and ontogeny of sulfotransferase enzymes in mice.
Toxicol Sci. 2006 Oct;93(2):242-55. doi: 10.1093/toxsci/kfl050. Epub 2006 Jun 28.

引用本文的文献

2
Update of the scientific opinion on tetrabromobisphenol A (TBBPA) and its derivatives in food.
EFSA J. 2024 Jul 15;22(7):e8859. doi: 10.2903/j.efsa.2024.8859. eCollection 2024 Jul.
3
Cytosolic sulfotransferases in endocrine disruption.
Essays Biochem. 2024 Dec 4;68(4):541-553. doi: 10.1042/EBC20230101.
4
Complex roles for sulfation in the toxicities of polychlorinated biphenyls.
Crit Rev Toxicol. 2024 Feb;54(2):92-122. doi: 10.1080/10408444.2024.2311270. Epub 2024 Feb 16.
6
7
Inhibition of Human Sulfotransferases by Phthalate Monoesters.
Front Endocrinol (Lausanne). 2022 Apr 22;13:868105. doi: 10.3389/fendo.2022.868105. eCollection 2022.
10
Stress, Sex, and Sugar: Glucocorticoids and Sex-Steroid Crosstalk in the Sex-Specific Misprogramming of Metabolism.
J Endocr Soc. 2020 Jul 3;4(8):bvaa087. doi: 10.1210/jendso/bvaa087. eCollection 2020 Aug 1.

本文引用的文献

1
Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development.
Drug Metab Dispos. 2018 Aug;46(8):1146-1156. doi: 10.1124/dmd.118.081398. Epub 2018 Jun 1.
4
Sulphation of acetaminophen by the human cytosolic sulfotransferases: a systematic analysis.
J Biochem. 2015 Dec;158(6):497-504. doi: 10.1093/jb/mvv062. Epub 2015 Jun 11.
6
Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.
Toxicol Appl Pharmacol. 2014 Jan 15;274(2):263-73. doi: 10.1016/j.taap.2013.11.009. Epub 2013 Nov 22.
8
Studies on RNA integrity and gene expression in human myocardial tissue, pericardial fluid and blood, and its postmortem stability.
Forensic Sci Int. 2013 Oct 10;232(1-3):218-28. doi: 10.1016/j.forsciint.2013.08.001. Epub 2013 Aug 15.
9
Expression of the sulfotransferase 1C family: implications for xenobiotic toxicity.
Drug Metab Rev. 2013 Nov;45(4):450-9. doi: 10.3109/03602532.2013.835634. Epub 2013 Sep 12.
10
Prenatal exposure to the pesticide DDT and hypertension diagnosed in women before age 50: a longitudinal birth cohort study.
Environ Health Perspect. 2013 May;121(5):594-9. doi: 10.1289/ehp.1205921. Epub 2013 Mar 12.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验