Downregulation of sulfotransferase expression and activity in diseased human livers

Emine B. Yalcin, Vijay More, Karissa L. Neira, Zhenqiang James Lu, Nathan J. Cherrington, Angela L. Slitt, Roberta S. King

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Sulfotransferase (SULT) function has been well studied in healthy human subjects by quantifying mRNA and protein expression and determining enzyme activity with probe substrates. However, it is not well known if sulfotransferase activity changes in metabolic and liver disease, such as diabetes, steatosis, or cirrhosis. Sulfotransferases have significant roles in the regulation of hormones and excretion of xenobiotics. In the present study of normal subjects with nonfatty livers and patients with steatosis, diabetic cirrhosis, and alcoholic cirrhosis, we sought to determine SULT1A1, SULT2A1, SULT1E1, and SULT1A3 activity and mRNA and protein expression in human liver tissue. In general, sulfotransferase activity decreased significantly with severity of liver disease from steatosis to cirrhosis. Specifically, SULT1A1 and SULT1A3 activities were lower in disease states relative to nonfatty tissues. Alcoholic cirrhotic tissues further contained lower SULT1A1 and 1A3 activities than those affected by either of the two other disease states. SULT2A1, on the other hand, was only reduced in alcoholic cirrhotic tissues. SULT1E1 was reduced both in diabetic cirrhosis and in alcoholic cirrhosis tissues, relative to nonfatty liver tissues. In conclusion, the reduced levels of sulfotransferase expression and activity in diseased versus nondiseased liver tissue may alter the metabolism and disposition of xenobiotics and affect homeostasis of endobiotic sulfotransferase substrates.

Original languageEnglish (US)
Pages (from-to)1642-1650
Number of pages9
JournalDrug Metabolism and Disposition
Volume41
Issue number9
DOIs
StatePublished - Sep 1 2013

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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