Expression of glutathione S-transferases in rat brains

Abstract

The tissue-specific expression of glutathione S-transferase (GSTs) in rat brains has been studied by protein purification, in vitro translation of brain poly (A) RNAs, and RNA blot hybridization with cDNA clones of the Y(a), Y(b), and Y(c) subunit of rat liver GSTs. Four classes of GST subunits are expressed in rat brains at M(r) 28,000 (Y)(c), M(r) 27,000 (Y)(b), M(r) 26,300, and M(r) 25,000. The M(r) 26,300 species, or Y(β), has an electrophoretic mobility between that of Y(a) and Y(b), similar to the liver Y(n) subunit(s) reported by Hayes (Hayes, J.D. (1984) Biochem. J. 224, 839-852). RNA blot hybridization of brain poly(A) RNAs with a liver Y(b) cDNA probe revealed two RNA species of ~1300 and ~1100 nucleotides. The band at ~1300 nucleotides was absent in liver poly(A) RNAs. The M(r) 25,000 species, or Y(δ) can be immunoprecipitated by antisera against rat heart and rat testis GSTs, but not by antiserum against rat liver GSTs. Therefore, the Y(δ) subunit may be related to the 'M(r) 22,000 subunit reported by Tu et al. (Tu, C.-P.D., Weiss, M.J., Li, N., and Reddy, C.C. (1983) J. Biol. Chem. 258, 4659-4662). The abundant liver GST subunits, Y(a), are not expressed in rat brains as demonstrated by electrophoresis of purified brain GSTs and a lack of isomerase activity toward the Y(a)-specific substrate, Δ5-androstene-3, 17-dione. This is apparently because of the absence of Y(a) mRNA expression prior to RNA processing. The data on the preferential expression of Y(c) subunits in rat brains, together with the differential phenobarbital inducibility of the Y(a) subunit(s) in rat liver reported by Pickett et al. (Pickett, C.B., Donohue, A.M., Lu, A.Y.H., and Hales, B.F. (1982) Arch. Biochem. Biophys. 215, 539-543), suggest that the Y(a) and Y(c) genes for rat GSRs are two functionally distinct gene families even though they share 68% DNA sequence homology. The expression of multiple GSTs in rat brains suggests that GSTs may be involved in physiological processes other than xenobiotics metabolism.