Interferon- and streptolysin O-induced activation of protein kinases and inhibition of cytochrome P450-dependent monooxygenases in rats.
Immunostimulants known to initiate cytokine production were found to decrease the activity of hepatic microsomal drug oxidative enzymes but to activate protein kinase C (PKC). The present study investigated the effects of immunostimulating doses of rat interferon-gamma (IFN, 670,000 units i.p.) and streptolysin O (SLO, 100 HU/kg i.v. for 5 days) on hepatic soluble, membrane-bound and nuclear PKC, 7-ethylresorufin-O-deethylase (EROD) and 7-pentylresorufin-O-deethylase (PROD) in male Wistar rats. The SLO- and IFN-mediated decrease of EROD and PROD activity was associated with a characteristic activation of the hepatic and spleenic PKC. In SLO- and IFN-treated animals activities of the cytosolic, membrane-bound and nuclear PKC were significantly higher than in respective controls. Our results suggest that a decrease in hepatic cytochrome P450 content as well as the decrease in the EROD and PROD activities are inversely related to the function of PKC.
Möritz
K U
KU
Institut für Pharmakologie, Ernst-Moritz-Arndt-Universität Greifswald, Germany.
Walter
R
R
Leopold
K
K
Hadasová
E
E
Engel
G
G
Siegmund
W
W
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009929:Organ Size / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013154:Spleen / Q000187:drug effects / Q000201:enzymology; D013301:Streptolysins / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011994:Recombinant Proteins; D013301:Streptolysins; C025964:streptolysin O; D007371:Interferon-gamma; D006899:Mixed Function Oxygenases; D011494:Protein Kinases; D011493:Protein Kinase C