HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bhat, R. Articles by Bresnick, E. Search for Related Content PubMed PubMed Citation Articles by Bhat, R. Articles by Bresnick, E. Social Bookmarking                      What's this?

Volume 272, Number 34, Issue of August 22, 1997 pp. 21221-21226
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Glycine N-Methyltransferase Is an Example of Functional Diversity
ROLE AS A POLYCYCLIC AROMATIC HYDROCARBON-BINDING RECEPTOR

(Received for publication, December 30, 1996, and in revised form, April 14, 1997)

From the Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655

The cytochrome P-4501A1 (CYP1A1) gene is regulated by several trans-acting factors including the 4 S polycyclic aromatic hydrocarbon (PAH)-binding protein, which has recently been identified as glycine N-methyltransferase (GNMT) (Raha, A., Wagner, C., Macdonald, R. G., and Bresnick, E. (1994) J. Biol. Chem. 269, 5750-5756). The role of GNMT as a 4 S PAH-binding protein in mediating the induction of cytochrome P-4501A1 has been investigated further. GNMT cDNA, which was cloned into a pMAMneo vector containing the Rous sarcoma virus promoter and the neomycin resistance gene, was stably transfected into D422 Chinese hamster ovary (CHO) cells. Several positive clones were selected by reverse transcription-polymerase chain reaction and assayed for the expression of recombinant protein. Western blot analysis indicated the expression of significant levels of the 4 S protein in the stably transfected CHO cells (CHO-GNMT). Cytosolic preparations from the CHO-GNMT showed high benzo[a]pyrene (B[a]P) binding but no 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) binding activity when compared with clones transfected with the pMAMneo vector alone (CHO-neo) or the parental CHO cells. Challanging the CHO-GNMT cells with 4 µM B[a]P resulted in elevated levels of CYP1A1 mRNA. Equally effective in inducing CYP1A1 mRNA were benzo[e]pyrene and 3-methylcholanthrene. On the other hand, TCDD did not induce CYP1A1 gene expression in these cells. B[a]P-treated CHO-GNMT, expressing the 4 S protein, also showed CYP1A1 protein by Western blotting and exhibited ethoxyresorufin-O-deethylase activity; neither the CHO-neo or parental CHO cells were positive for any of these measures. No Ah receptor message or protein was detectable in the parental CHO, CHO-neo, or CHO-GNMT cells. Furthermore, no XRE binding activity was observed in TCDD-treated cytosolic preparations or nuclear extracts from CHO-GNMT cells that were treated with TCDD. These studies unequivocally establish that GNMT is a PAH-binding protein that can mediate the induction of CYP1A1 by PAHs such as B[a]P through an Ah receptor-independent pathway.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. B. Okey An Aryl Hydrocarbon Receptor Odyssey to the Shores of Toxicology: The Deichmann Lecture, International Congress of Toxicology-XI Toxicol. Sci., July 1, 2007; 98(1): 5 - 38. [Abstract] [Full Text] [PDF]

				Y.-C. Huang, C.-M. Lee, M. Chen, M.-Y. Chung, Y.-H. Chang, W. J.-S. Huang, D. M.-T. Ho, C.-C. Pan, T. T. Wu, S. Yang, et al. Haplotypes, Loss of Heterozygosity, and Expression Levels of Glycine N-Methyltransferase in Prostate Cancer Clin. Cancer Res., March 1, 2007; 13(5): 1412 - 1420. [Abstract] [Full Text] [PDF]

				T.-L. Tseng, Y.-P. Shih, Y.-C. Huang, C.-K. Wang, P.-H. Chen, J.-G. Chang, K.-T. Yeh, Y.-M. A. Chen, and K. H. Buetow Genotypic and Phenotypic Characterization of a Putative Tumor Susceptibility Gene, GNMT, in Liver Cancer Cancer Res., February 1, 2003; 63(3): 647 - 654. [Abstract] [Full Text] [PDF]

				M. J. Rowling, M. H. McMullen, D. C. Chipman, and K. L. Schalinske Hepatic Glycine N-Methyltransferase Is Up-Regulated by Excess Dietary Methionine in Rats J. Nutr., September 1, 2002; 132(9): 2545 - 2550. [Abstract] [Full Text] [PDF]

				Y.-T. Hou, H.-K. Lin, and T. M. Penning Dexamethasone Regulation of the Rat 3alpha -Hydroxysteroid/Dihydrodiol Dehydrogenase Gene Mol. Pharmacol., March 1, 1998; 53(3): 459 - 466. [Abstract] [Full Text]