GLUTATHIONE-DEPENDENT PROTECTION AGAINST LIPID-PEROXIDATION IN SHEEP LIVER-MICROSOMES

In the present studies we have described a glutathione-dependent syste m in sheep liver microsomes that protects against membrane lipid perox idation initiated by either Fe+2/NADPH or Fe+2/ascorbate. Glutathione protected against lipid peroxidation in microsomes containing a wide r ange of a-tocopherol levels (0.02-0.11 mu g/mg protein). The addition of glutathione disulfide alone had no effect on microsomal lipid perox idation; however, it prolonged the protection afforded by glutathione, particularly in assays containing Fe+2/NADPH. Whereas the glutathione -dependent protection was very labile, with loss of activity demonstra ted in microsomes stored at 4 degrees C for 24 hours, the combined eff ect of glutathione and glutathione disulfide was not affected by stora ge; The glutathione S-transferase inhibitors, bromosulphothalein and S -hexylglutathione, reversed the protection observed with glutathione, indicating a possible role for microsomal glutathione S-transferases i n this protection, but not that observed by the combination of glutath ione and glutathione disulfide. In general, our findings support previ ous results observed with rat liver microsomes and suggest that micros omal glutathione S-transferases may be involved in the glutathione-dep endent protection in sheep liver microsomes.