Several closely related glutathione S-transferase isozymes catalyzing conjugation of 4-hydroxynonenal are differentially expressed in human tissues.
A human acidic glutathione S-transferase, hGST 5.8, was isolated from heart, pancreas, and brain by a procedure involving immunoadsorption chromatography 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-chloro-2,4-dinitrobenzene, and expressed glutathione peroxidase activity toward phospholipid hydroperoxides. In this respect, the enzymes belong 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 from various human tissues revealed significant similarity to mGSTA4-4 and the existence of several distinct isoforms differing in their primary structures. These isoforms had similar but nevertheless clearly distinguishable catalytic properties. These results indicate the existence of multiple hGST 5.8-related genes in the humans, which is consistent with our previous studies showing the presence of several closely related genes for the mouse ortholog mGSTA4-4 (Zimniak et al., J. Biol. Chem., 1994, 269, 992-1000).
Singhal
S S
SS
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555.
Zimniak
P
P
Awasthi
S
S
Piper
J T
JT
He
N G
NG
Teng
J I
JI
Petersen
D R
DR
Awasthi
Y C
YC
D000447:Aldehydes / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002846:Chromatography, Affinity; D016384:Consensus Sequence; D005260:Female; D015870:Gene Expression; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology*; D009928:Organ Specificity; D010179:Pancreas / Q000201:enzymology*; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D010449:Peptide Mapping; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D000447:Aldehydes; D007527:Isoenzymes; D010446:Peptide Fragments; D005982:Glutathione Transferase; C027576:4-hydroxy-2-nonenal