Activity of rat liver microsomal glutathione transferase toward products of lipid peroxidation and studies of the effect of inhibitors on glutathione-dependent protection against lipid peroxidation.
Rat liver microsomal glutathione transferase displays glutathione peroxidase activity with linoleic acid hydroperoxide, linoleic acid ethyl ester hydroperoxide, and dilinoleoyl phosphatidylcholine hydroperoxide, with rates of 0.2, 0.3, and 0.3 mumol/min/mg, respectively. The activities are increased between three- and fourfold when the enzyme is activated with N-ethylmaleimide. Microsomal glutathione transferase can also conjugate 4-hydroxynon-2-enal with a specific activity of 0.5 mumol/min/mg. These findings show that the enzyme can remove harmful products of lipid peroxidation and thereby possibly protect intracellular membranes against oxidative stress. A set of glutathione transferase inhibitors (rose bengal, tributyltin acetate, S-hexylglutathione, indomethacin, cibacron blue, and bromosulfophtalein) which abolish the glutathione-dependent protection against lipid peroxidation in liver microsomes have been characterized. These inhibitors were found to be effective in the micromolar range and could prove valuable in studying the factor responsible for glutathione-dependent protection against lipid peroxidation.
Mosialou
E
E
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Morgenstern
R
R
D000818:Animals; D005978:Glutathione / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology*; D008954:Models, Biological; D051381:Rats; D013379:Substrate Specificity
D008054:Lipid Peroxides; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione