SEVERAL CLOSELY-RELATED GLUTATHIONE-S-TRANSFERASE ISOZYMES CATALYZINGCONJUGATION OF 4-HYDROXYNONENAL ARE DIFFERENTIALLY EXPRESSED IN HUMANTISSUES

A human acidic glutathione S-transferase, hGST 5.8, was isolated from heart, pancreas, and brain by a procedure involving immunoadsorption c hromatography on immobilized antibodies raised against mouse mGSTA4-4. The human hGST 5.8 enzymes isolated from these tissues had similar pI (5.8) and subunit M(r) (24.5 kDa) values, showed about 17- to 20-fold higher specific activities for 4-hydroxynon-2-enal than that for 1-ch loro-2 4-dinitrobenzene, and expressed glutathione peroxidase activity toward phospholipid hydroperoxides. In this respect, the enzymes belo ng together with rat GST 8-8 and mouse mGSTA4-4 to a subgroup of GSTs involved in the detoxification of lipid peroxidation products. Partial sequencing of CNBr-peptide fragments of hGST 5.8 proteins isolated fr om various human tissues revealed significant similarity to mGSTA4-4 a nd the existence of several distinct isoforms differing in their prima ry structures. These isoforms had similar but nevertheless clearly dis tinguishable catalytic properties. These results indicate the existenc e of multiple hGST 5.8-related genes in the humans, which is consisten t with our previous studies showing the presence of several closely re lated genes for the mouse ortholog mGSTA4-4 (Zimniak ct al;, J. Biol. Chem., 1994, 269, 992-1000). (C) 1994 Academic Press, Inc.