NDLI: Drug-Metabolizing Activity, Protein and Gene Expression of UDP-Glucuronosyltransferases Are Significantly Altered in Hepatocellular Carcinoma Patients

Content Provider	PubMed Central
Author	Lu, Linlin Zhou, Juan Shi, Jian Peng, Xiao-juan Qi, Xiao-xiao Wang, Ying Li, Fang-yuan Zhou, Fu-yuan Liu, Liang Liu, Zhong-qiu
Editor	Sun, Qinghua
Copyright Year	2015
Abstract	UDP-glucuronosyltransferases (UGTs), the most important enzymes in body detoxification and homeostasis maintaining, govern the glucuronidation reaction of various endogenous and environmental carcinogens. The metabolic function of UGTs can be severely influenced by hepatocellular carcinoma (HCC), the fifth prevalent and third malignant cancer worldwide. Particularly in China, HBV-positive HCC account for approximately 80% of HCC patients. But rare papers addressed the alteration on the metabolism of UGTs specific substrates, translational and transcriptional activity of UGTs in HBV-positive HCC patients. In present study, we choose the main UGT isoforms, UGT1As, UGT1A1, UGT1A9, UGT1A4 and UGT2B7, to determine the alterations of metabolic activity, protein and gene expression of UGTs in HBV-positive HCC. The corresponding specific substrates such as genistein, SN-38, tamoxifen, propofol and zidovudine were utilized respectively in UGTs metabolic activity determination. Furthermore, the plausible mechanism responsible for UGTs alterations was addressed by analyzing the protein and gene expressions in tumor and the adjacent normal tissues in HBV-positive HCC. The results revealed that in the tumor human liver microsomes (HLMs), either Vmax (maximum reaction rate, Rmax for UGT1A1) or the clearance rates (Vmax/Km, Clint) of UGT1A, UGT1A1, UGT1A4, UGT1A9 and UGT2B7 were significant lower than those of in the adjacent normal HLMs. Subsequently, the relative protein and gene expressions of these isoforms were notably decreased in most of tumor tissues comparing with the adjacent normal tissues. More interestingly, in tumor tissues, the metabolic activity reduction ratio of each UGT isoform was closely related to its protein reduction ratio, indicating that decreasing protein level would contribute to the reduced metabolic function of UGTs in HBV-positive HCC. In summary, our study firstly determined the alteration of UGT function in HBV-positive HCC patients, which would provide an important insight for toxicity or efficacy determination of chemotherapeutic drugs, and even bring a new strategy for clinical regimen in the health cares for the relative patients.
Related Links	http://dx.doi.org/10.1371/journal.pone.0127524
Starting Page	127524
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	5
Volume Number	10
Language	English
Publisher	Public Library of Science
Publisher Date	2015-05-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Sorafenib Metabolism Is Significantly Altered in the Liver Tumor Tissue of Hepatocellular Carcinoma Patient

Albumin Stimulates the Activity of the Human UDP-Glucuronosyltransferases 1A7, 1A8, 1A10, 2A1 and 2B15, but the Effects Are Enzyme and Substrate Dependent

Increased Expression of Yes-Associated Protein 1 in Hepatocellular Carcinoma with Stemness and Combined Hepatocellular-Cholangiocarcinoma

Urinary Collagen Fragments Are Significantly Altered in Diabetes: A Link to Pathophysiology

Gene Expression-Based Chemical Genomics Identifies Potential Therapeutic Drugs in Hepatocellular Carcinoma

Global Gene Expression Profiling Reveals SPINK1 as a Potential Hepatocellular Carcinoma Marker

Axl Expression Stratifies Patients with Poor Prognosis after Hepatectomy for Hepatocellular Carcinoma

A Quantitative Proteomic Approach to Identify Significantly Altered Protein Networks in the Serum of Patients with Lymphangioleiomyomatosis (LAM)

OPN and αvβ3 Expression are Predictors of Disease Severity and Worse Prognosis in Hepatocellular Carcinoma

Drug-Metabolizing Activity, Protein and Gene Expression of UDP-Glucuronosyltransferases Are Significantly Altered in Hepatocellular Carcinoma Patients

Similar Documents

Sorafenib Metabolism Is Significantly Altered in the Liver Tumor Tissue of Hepatocellular Carcinoma Patient

Albumin Stimulates the Activity of the Human UDP-Glucuronosyltransferases 1A7, 1A8, 1A10, 2A1 and 2B15, but the Effects Are Enzyme and Substrate Dependent

Increased Expression of Yes-Associated Protein 1 in Hepatocellular Carcinoma with Stemness and Combined Hepatocellular-Cholangiocarcinoma

Urinary Collagen Fragments Are Significantly Altered in Diabetes: A Link to Pathophysiology

Gene Expression-Based Chemical Genomics Identifies Potential Therapeutic Drugs in Hepatocellular Carcinoma

Global Gene Expression Profiling Reveals SPINK1 as a Potential Hepatocellular Carcinoma Marker

Axl Expression Stratifies Patients with Poor Prognosis after Hepatectomy for Hepatocellular Carcinoma

A Quantitative Proteomic Approach to Identify Significantly Altered Protein Networks in the Serum of Patients with Lymphangioleiomyomatosis (LAM)

OPN and αvβ3 Expression are Predictors of Disease Severity and Worse Prognosis in Hepatocellular Carcinoma

Drug-Metabolizing Activity, Protein and Gene Expression of UDP-Glucuronosyltransferases Are Significantly Altered in Hepatocellular Carcinoma Patients