(S)-preferential detoxification of 4-hydroxy-2(E)-nonenal enantiomers by hepatic glutathione S-transferase isoforms in guinea-pigs and rats.
In guinea-pig liver cytosol, racemic 4-hydroxy-2(E)-nonenal (HNE), a reactive and highly toxic product released from biomembranes by lipid peroxidation, was detoxified (S)-preferentially by GSH conjugation mediated by glutathione S-transferases (GSTs) and (R)-preferentially by NAD(+)-dependent oxidation mediated by aldehyde dehydrogenase (ALDH). The GST-mediated detoxification of the HNE enantiomers proceeded at much higher rates than that mediated by ALDH in guinea-pig liver cytosol. All the major guinea-pig GSTs, A1-1, M1-1, M1-2 and M1-3*, isolated from guinea-pig liver cytosol also catalysed the (S)-preferential conjugation of the HNE enantiomers. The liver and other major tissues of guinea-pigs had no immunologically detectable level of a putative GSTA4-4 orthologue, which exists as a minor GST protein in rat, mouse and human livers and exhibits extremely high catalytic activity towards HNE. All the hepatic rat GSTs, A1-1(2), A1-3, A4-4, M1-1, M1-2 and M2-2, also catalysed the (S)-preferential conjugation of HNE enantiomers.
Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392, Japan.
A
A
Hiratsuka
K
K
Tobita
H
H
Saito
Y
Y
Sakamoto
H
H
Nakano
K
K
Ogura
T
T
Nishiyama
T
T
Watabe
D000447:Aldehydes / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D015153:Blotting, Western; D002846:Chromatography, Affinity; D003600:Cytosol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000302:isolation & purification / Q000378:metabolism*; D006168:Guinea Pigs; D008658:Inactivation, Metabolic; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D000447:Aldehydes; D007527:Isoenzymes; D005982:Glutathione Transferase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal