Distribution of microsomal glutathione transferase 1 in mammalian tissues - A predominant alternate first exon in human tissues

An extensive Northern blot analysis of microsomal glutathione transferase I in human and rat tissues was performed. When normalized against the glycer aldehyde-3-phosphate dehydrogenase or actin expression it was evident that the predominant expression occurs in liver and pancreas. An ontogenetic, as well as a functional, basis for the high levels in these two organs is pos sible. The relative expression levels in man ranged from: liver and pancrea s (100%), to kidney prostate, colon (30-40%), heart, brain, lung, testis, o vary, small intestine (10-20%), placenta, skeletal muscle, spleen, thymus a nd peripheral blood leucocytes (1-10%). Liver-enriched expression was detec ted in human fetal tissues with lung and kidney displaying lower levels (10 -20%). No transcripts could be detected in fetal brain or heart. When compa ring the expression levels between rat and man it is apparent that human ex trahepatic mRNA levels are much higher relative to liver. Rat microsomal gl utathione transferase mRNA expression ranges from 0.2 to 10% that of liver, with adrenal, uterus, ovary and stomach displaying the highest levels of t he organs tested. Based on these observations, and the fact that the enzyme is encoded by a highly conserved single-copy gene, it is suggested that mi crosomal glutathione transferase 1 performs essential functions vital to mo st mammalian cell types. We suggest that protection against oxidative stres s constitutes one such function. Human expressed sequence tag (EST) charact erization yielded four alternate mRNA transcripts with different 5'-ends (f our alternate noncoding exons 1). The predominant exon (based on the observ ed EST frequency) revealed a tissue distribution similar to that obtained u sing the reading frame as probe. Thus, it appears that one exon preferentia lly gives rise to mature mRNA in the human tissues examined. This exon is d ifferent from the one reported in the original cDNA characterized.