Linked Life Data

8460949

Source:http://linkedlifedata.com/resource/pubmed/id/8460949

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1993-4-23
pubmed:abstractText
Class mu glutathione S-transferases (GSTs) are important in the detoxication of epoxides generated by oxidative metabolism. Phenobarbital, 3-methylcholanthrene, and pyridine have failed to enhance the expression of class mu GST isozymes in rabbit hepatic tissue (T. Primiano, S. G. Kim, and R. F. Novak, Toxicol. Appl. Pharmacol., 113, 64-73, 1992). Two class mu GST isozymes have been isolated from rabbit hepatic cytosol and purified to homogeneity using S-hexylglutathione-agarose, CM-Sepharose, and PBE94 chromatofocusing chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses showed that both isozymes possessed M(r) values of approximately 25,500 and cross-reacted with class mu-specific GST IgG. Gel filtration analysis revealed that these isozymes were dimers with molecular weights of approximately 45 kDa. The class mu GST isozymes had pIs of 7.8 and 7.2 as determined by nonequilibrium pH gel electrophoresis. The class mu GST 7.8 and 7.2 isozymes exhibited different metabolic activities toward the substrates 1-chloro-2,4-dinitrobenzene, bromosulfophthalein, 1,2-epoxy-3-(p-nitrophenoxy)propane, trans-4-phenyl-3-buten-2-one, p-nitrobenzyl chloride, and 3,4-dichloronitrobenzene. Metabolic activity of the two GSTs toward the substrate 1-chloro-2,4-dinitrobenzene was inhibited by Cibacron blue, triethyltin bromide, S-hexylglutathione, bromosulfophthalein, and indomethacin. The amino acid composition of GST mu 7.8 and 7.2 was determined and found to be very similar to those of purified rat class mu GST isozymes. N-terminal analysis of the first 21 residues of the pI 7.8 class mu GST isozyme revealed that it had 71 and 81% sequence identity with the Yb1 and Yb2 subunits, respectively. Similarly, N-terminal analysis of the first 21 residues of the pI 7.2 class mu GST isozyme revealed a 75% sequence identity with either the rat Yb1 or Yb2 subunit. Examination of class mu GST expression in rabbit hepatic cytosol following treatment with a series of known inducers including phenobarbital, 3-methylcholanthrene, isosafrole, pyrazine, trans-stilbene oxide, butylated hydroxyanisole, and tert-butylhydroquinone was accomplished. The data show that these agents not only failed to enhance class mu GST expression, but that 3-methylcholanthrene and isosafrole caused suppression of class mu GSTs. These results provide evidence for the existence of two closely related class mu GST isozymes in rabbit hepatic tissue and suggest that the molecular mechanisms regulating GST expression differ between rat and rabbit in response to these xenobiotics.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:volume
301
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
404-10
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Purification and characterization of class mu glutathione S-transferase isozymes from rabbit hepatic tissue.
pubmed:affiliation
Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan 48201.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.