Linked Life Data

9261130

Source:http://linkedlifedata.com/resource/pubmed/id/9261130

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
1997-9-15
pubmed:abstractText
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 microM 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21221-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9261130-Animals, pubmed-meshheading:9261130-Benzo(a)pyrene, pubmed-meshheading:9261130-CHO Cells, pubmed-meshheading:9261130-Cricetinae, pubmed-meshheading:9261130-Cytochrome P-450 CYP1A1, pubmed-meshheading:9261130-DNA-Binding Proteins, pubmed-meshheading:9261130-Dimerization, pubmed-meshheading:9261130-Enzyme Induction, pubmed-meshheading:9261130-Gene Expression Regulation, Enzymologic, pubmed-meshheading:9261130-Glycine N-Methyltransferase, pubmed-meshheading:9261130-Methyltransferases, pubmed-meshheading:9261130-Promoter Regions, Genetic, pubmed-meshheading:9261130-Protein Binding, pubmed-meshheading:9261130-RNA, Messenger, pubmed-meshheading:9261130-Rats, pubmed-meshheading:9261130-Receptors, Aryl Hydrocarbon, pubmed-meshheading:9261130-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:9261130-Structure-Activity Relationship, pubmed-meshheading:9261130-Tetrachlorodibenzodioxin, pubmed-meshheading:9261130-Transcription, Genetic, pubmed-meshheading:9261130-Transfection
pubmed:year
1997
pubmed:articleTitle
Glycine N-methyltransferase is an example of functional diversity. Role as a polycyclic aromatic hydrocarbon-binding receptor.
pubmed:affiliation
Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.