The distribution, induction and isoenzyme profile of glutathione S-transferase and glutathione peroxidase in isolated rat liver parenchymal, Kupffer and endothelial cells.
The distribution and inducibility of cytosolic glutathione S-transferase (EC 2.5.1.18) and glutathione peroxidase (EC 1.11.1.19) activities in rat liver parenchymal, Kupffer and endothelial cells were studied. In untreated rats glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene and 4-hydroxynon-2-trans-enal as substrates was 1.7-2.2-fold higher in parenchymal cells than in Kupffer and endothelial cells, whereas total, selenium-dependent and non-selenium-dependent glutathione peroxidase activities were similar in all three cell types. Glutathione S-transferase isoenzymes in parenchymal and non-parenchymal cells isolated from untreated rats were separated by chromatofocusing in an f.p.l.c. system: all glutathione S-transferase isoenzymes observed in the sinusoidal lining cells were also detected in the parenchymal cells, whereas Kupffer and endothelial cells lacked several glutathione S-transferase isoenzymes present in parenchymal cells. At 5 days after administration of Arocolor 1254 glutathione S-transferase activity was only enhanced in parenchymal cells; furthermore, selenium-dependent glutathione peroxidase activity decreased in parenchymal and non-parenchymal cells. At 13 days after a single injection of Aroclor 1254 a strong induction of glutathione S-transferase had taken place in all three cell types, whereas selenium-dependent glutathione peroxidase activity remained unchanged (endothelial cells) or was depressed (parenchymal and Kupffer cells). Hence these results clearly establish that glutathione S-transferase and glutathione peroxidase are differentially regulated in rat liver parenchymal as well as non-parenchymal cells. The presence of glutathione peroxidase and several glutathione S-transferase isoenzymes capable of detoxifying a variety of compounds in Kupffer and endothelial cells might be crucial to protect the liver from damage by potentially hepatotoxic substances.
Steinberg
P
P
Institut für Toxikologie, Universität Mainz, Federal Republic of Germany.
Schramm
H
H
Schladt
L
L
Robertson
L W
LW
Thomas
H
H
Oesch
F
F
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D020111:Chlorodiphenyl (54% Chlorine); D003429:Cross Reactions; D004727:Endothelium / Q000201:enzymology; D004790:Enzyme Induction; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D007106:Immune Sera; D015151:Immunoblotting; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D007728:Kupffer Cells / Q000201:enzymology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001140:Aroclors; D007106:Immune Sera; D007527:Isoenzymes; D020111:Chlorodiphenyl (54% Chlorine); D005979:Glutathione Peroxidase; D005982:Glutathione Transferase