A basis for differentiating among the multiple human Mu-glutathione S-transferases and molecular cloning of brain GSTM5.

Apr 25, 1993The Journal of biological chemistry

Understanding differences between human Mu-glutathione S-transferase enzymes and cloning the brain version GSTM5

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Abstract

A cDNA probe identified three distinct transcripts in human tissues related to Mu-class glutathione S-transferases.

The smallest transcript identified at 1.3 kb encodes the GSTM3-3 subunits.
A newly cloned form, GSTM5, has a unique 846-nucleotide 3'-noncoding region compared to other Mu-class glutathione S-transferases.
The primary transcript in the liver is GSTM1-1, with lower levels of GSTM3-3, while GSTM2-2 and GSTM5-5 are absent.
Null-phenotype individuals lack the GSTM1 gene, not the nearly identical GSTM2 gene.
All four forms of Mu-class glutathione S-transferases are present in brain and testis tissues.

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Specific cDNA probes and antisera were employed to interpret genetic polymorphisms of human Mu-class glutathione S-transferases and to provide a basis for identifying individual forms in human tissues. A cDNA probe that cross-hybridized with various human and rodent Mu-glutathione S-transferase transcripts, hybridized with at least three discrete components by Northern analysis of RNA from human tissue. The smallest (1.3 kb) transcript was identified as the one that encodes GSTM3-3 subunits. A form designated GSTM5, was cloned from a human brain cDNA library and its sequence determined. The open reading frame of GSTM5 shared a high degree of homology with the sequences of other Mu-class glutathione S-transferases, but its 846-nucleotide 3'-noncoding region was unique and considerably larger than that of any of the other Mu forms. Specific synthetic peptide antigens were utilized to distinguish among Mu-class glutathione S-transferases in different tissues of representative individuals. The primary hepatic transcript was that encoding GSTM1-1 with much lesser amounts of GSTM3-3, but livers were devoid of GSTM2-2, and GSTM5-5. Immunoblots confirmed that null-phenotype individuals lacked the GSTM1 gene rather than its GSTM2 homologue that is nearly identical in its exon sequences. The null phenotype therefore was conspicuous in liver, where GSTM1-1 ordinarily was the predominant Mu transcript, but brain and testis contained all four forms. A general strategy was devised to distinguish among and assign primary structures to individual glutathione S-transferases from human tissue.

A basis for differentiating among the multiple human Mu-glutathione S-transferases and molecular cloning of brain GSTM5.

Abstract

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