Four distinct membrane-bound dipeptidase RNAs are differentially expressed and show discordant regulation with gamma-glutamyl transpeptidase.
Membrane-bound dipeptidase (MBD) participates in the degradation of glutathione by cleaving the cysteinyl-glycine bond of cystinyl bisglycine (oxidized cysteinyl-glycine) following removal of a gamma-glutamyl group by gamma-glutamyl transpeptidase (GGT). In the mouse, MBD RNA is most abundant in small intestine, kidney, and lung and is represented by four distinct RNA species. These are generated by transcription from two promoters located 6 kilobases apart in the 5' flanking region of the gene and by the use of two different poly(A) addition sites. Promoter I is used primarily in small intestine and kidney, whereas promoter II is most active in lung and kidney. We found a discordance in the expected co-expression of MBD and GGT; as expected, MBD and GGT are both expressed at high levels in the kidney and small intestine. However, in the lung, MBD is expressed at high levels, whereas GGT is almost undetectable. The reverse is true in the seminal vesicles and fetal liver. Thus, although both enzymes may function in concert to metabolize glutathione in kidney and small intestine, in other tissues they appear to act independently, suggesting that they have independent roles in other biological processes.
Habib
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GM
Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
Barrios
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R
Shi
Z Z
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Lieberman
M W
MW
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000201:enzymology; D017931:DNA Primers; D015342:DNA Probes; D004150:Dipeptidases / Q000096:biosynthesis* / Q000235:genetics*; D005091:Exons; D015971:Gene Expression Regulation, Enzymologic; D017403:In Situ Hybridization; D007421:Intestine, Small / Q000201:enzymology; D007438:Introns; D007668:Kidney / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis*; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D012669:Seminal Vesicles / Q000201:enzymology; D014158:Transcription, Genetic; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D017931:DNA Primers; D015342:DNA Probes; D012333:RNA, Messenger; D005723:gamma-Glutamyltransferase; D004150:Dipeptidases