Protein kinase C involvement in lipid peroxidation and cell membrane damage induced by oxygen-based radicals in hepatocytes.
We investigated the effects of oxygen-based radicals induced by t-butyl hydroperoxide or H2O2/Cu2+ on cultured hepatocytes. Radical exposure caused membrane lesions (blebs), lactate dehydrogenase release and lipid peroxidation (i.e. formation of malondialdehyde) in cells. As expected, radical scavengers (catalase, alpha-tocopherol) strongly inhibited these phenomena. A similar or even superior inhibitory effect was achieved by the protein kinase C (PKC) inhibitors H-7 and phloretin. These agents did not reveal notable radical scavenging properties as assessed by their ability to break down H2O2. The PKC stimulators 4 beta-phorbol-12-myristate-13 and 1-olyeoyl-2-acetyl-sn-glycerol intensified the detrimental actions of the radical-inducing agents. [3H]Phorbol-12,13-dibutyrate-binding studies showed that membrane association of PKC is markedly increased in hepatocytes after exposure to H2O2/Cu2+ or t-butyl hydroperoxide. These results suggest that PKC membrane translocation and activation may be important for mediating membrane damage and lipid peroxidation after cells are exposed to oxygen-based radicals.
von Ruecker
A A
AA
Department of Clinical Biochemistry, University of Bonn, Fed. Rep. Germany.
Han-Jeon
B G
BG
Wild
M
M
Bidlingmaier
F
F
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D005609:Free Radicals; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D010100:Oxygen / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D005609:Free Radicals; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; D010100:Oxygen