DMD

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Honma, W.
Right arrow Articles by Yamazoe, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Honma, W.
Right arrow Articles by Yamazoe, Y.

Vol. 30, Issue 8, 944-949, August 2002

Phenol Sulfotransferase, ST1A3, as the Main Enzyme Catalyzing Sulfation of Troglitazone in Human Liver

Wataru Honma, Miki Shimada, Hironobu Sasano, Shogo Ozawa, Masaaki Miyata, Kiyoshi Nagata, Toshihiko Ikeda, and Yasushi Yamazoe

Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan (W.H., M.S., M.M., K.N., and Y.Y.); Department of Anatomic Pathology, School of Medicine, Tohoku University, Sendai, Japan (H.S.); Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan (S.O.); and Pharmacokinetics and Drug Delivery Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan (T.I.)

Since sulfation is the main metabolic pathway of troglitazone, accounting for about 70% of the metabolites detected in human plasma, we have aimed to identify human cytosolic sulfotransferases catalyzing the sulfation of troglitazone and to examine a possible role of the sulfation in the cytotoxicity observed in cell lines of human origin (HepG2 and Hep3B). Experiments using the recombinant sulfotransferases and human liver cytosols indicated that phenol sulfotransferase (ST1A3) and estrogen sulfotransferase (ST1E4) were the sulfotransferases most active toward troglitazone. Immunoblot analyses indicated that hepatic content of ST1A3 is about 13 times higher than that of ST1E4, suggesting that ST1A3 is mainly responsible for the sulfation of troglitazone in the liver. Lactate dehydrogenase (LDH) leakage was elicited by troglitazone in a concentration-dependent manner in the hepatoma cells. The troglitazone metabolites (the sulfate, glucuronide, and quinone forms) caused negligible LDH leakage. These findings suggest that accumulation of unmetabolized troglitazone causes the cytotoxicity in the hepatoma cells and may be responsible for toxicity in human liver.

Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
J. Enokizono, H. Kusuhara, and Y. Sugiyama
Involvement of Breast Cancer Resistance Protein (BCRP/ABCG2) in the Biliary Excretion and Intestinal Efflux of Troglitazone Sulfate, the Major Metabolite of Troglitazone with a Cholestatic Effect
Drug Metab. Dispos., February 1, 2007; 35(2): 209 - 214.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
Z. Duanmu, A. Weckle, S. B. Koukouritaki, R. N. Hines, J. L. Falany, C. N. Falany, T. A. Kocarek, and M. Runge-Morris
Developmental Expression of Aryl, Estrogen, and Hydroxysteroid Sulfotransferases in Pre- and Postnatal Human Liver
J. Pharmacol. Exp. Ther., March 1, 2006; 316(3): 1310 - 1317.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
M. Katoh, T. Matsui, H. Okumura, M. Nakajima, M. Nishimura, S. Naito, C. Tateno, K. Yoshizato, and T. Yokoi
EXPRESSION OF HUMAN PHASE II ENZYMES IN CHIMERIC MICE WITH HUMANIZED LIVER
Drug Metab. Dispos., September 1, 2005; 33(9): 1333 - 1340.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Miyata, A. Tozawa, H. Otsuka, T. Nakamura, K. Nagata, F. J. Gonzalez, and Y. Yamazoe
Role of Farnesoid X Receptor in the Enhancement of Canalicular Bile Acid Output and Excretion of Unconjugated Bile Acids: A Mechanism for Protection against Cholic Acid-Induced Liver Toxicity
J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 759 - 766.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
M. L. Schrag, D. Cui, T. H. Rushmore, M. Shou, B. Ma, and A. D. Rodrigues
SULFOTRANSFERASE 1E1 IS A LOW KM ISOFORM MEDIATING THE 3-O-SULFATION OF ETHINYL ESTRADIOL
Drug Metab. Dispos., November 1, 2004; 32(11): 1299 - 1303.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
L.-Q. Wang, C. N. Falany, and M. O. James
TRICLOSAN AS A SUBSTRATE AND INHIBITOR OF 3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE-SULFOTRANSFERASE AND UDP-GLUCURONOSYL TRANSFERASE IN HUMAN LIVER FRACTIONS
Drug Metab. Dispos., October 1, 2004; 32(10): 1162 - 1169.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics.