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The Role of Sulfotransferase 2B1b in Acetaminophen-induced Liver injury

An, Yunqi (2018) The Role of Sulfotransferase 2B1b in Acetaminophen-induced Liver injury. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Overdose of acetaminophen (APAP) is the leading cause of acute liver failure (ALF). Although mechanisms of APAP-induced liver injury are well known, those that affect the progression of APAP-induced liver disease and facilitate liver recovery are less understood. The sulfotransferase 2B1b (SULT2B1b) participates various of liver relative diseases including metabolic syndrome, chronic liver injury and hepatocellular carcinoma. Our previous study showed that SULT2B1b is transcriptional regulated by Hepatic Nuclear Factor 4α (HNF4α), which is essential for liver development and function. However, the importance of SULT2B1b in APAP-induced acute liver injury remains unknown. In this study, we examined the role of SULT2B1b in APAP-induced hepatotoxicity. We showed that hepatic overexpression of SULT2B1b in liver sensitized mice to APAP-induced liver injury, whereas ablation of Sult2B1b conferred resistance to the APAP hepatotoxicity. Indeed, upregulation of Sult2B1b by Hnf4α in wild type mice showed more severe liver injury and this effect was abolished in Sult2B1b knockout mice evidenced by comparable liver damage. Therefore, we conclude that SULT2B1b represents a potential therapeutic target for the prevention and treatment of APAP-induced acute liver injury.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
An, Yunqiyua8@pitt.eduyua80000-0002-5789-7264
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairXie, Wenwex6@pitt.edu
Committee MemberMa, XiaochaoMXIAOCHA@pitt.edu
Committee MemberLi, Songsol4@pitt.edu
Date: 9 April 2018
Date Type: Publication
Defense Date: 14 March 2018
Approval Date: 9 April 2018
Submission Date: 5 April 2018
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 39
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: sulfotransferase; HNF4α; acetaminophen; liver injury
Date Deposited: 09 Apr 2018 15:12
Last Modified: 09 Apr 2018 15:12
URI: http://d-scholarship.pitt.edu/id/eprint/34117

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