Radiation-induced translocation of protein kinase C through membrane lipid peroxidation in primary cultured rat hepatocytes.
A mechanism of radiation-induced activation of protein kinase C was investigated in primary cultured rat hepatocytes. Irradiation of hepatocytes with 5 Gy or 50 Gy of gamma-rays caused an immediate and transient increase in the activity of protein kinase C in the membrane fraction, and a decrease in this activity in the cytosol fraction. A ligand binding procedure for protein kinase C using [3H]PDBu demonstrated that PDBu binding content increased in the membrane fraction and decreased in the cytosol fraction following irradiation. These results suggest that protein kinase C molecules were translocated from cytosol to the membrane after irradiation of the hepatocytes. Irradiation also induced lipid peroxidation of hepatocytes in the range from 0 to 50 Gy in a radiation dose-dependent fashion. This induction of lipid peroxidation was markedly suppressed by the addition of Trolox, a radical scavenger. Treatment of hepatocytes with Trolox also caused simultaneous inhibition of the radiation-induced increase in the PDBu binding content of the membrane fraction. We conclude that radiation-induced activation of protein kinase C results from the translocation of protein kinase C from cytosol to membrane due to membrane lipid peroxidation through reactive oxygen species produced by radiation.
Nakajima
T
T
Division of Biology and Oncology, National Institute of Radiological Sciences, Chiba-shi, Japan.
Yukawa
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O
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology / Q000528:radiation effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology / Q000528:radiation effects; D015227:Lipid Peroxidation / Q000528:radiation effects*; D008099:Liver / Q000201:enzymology* / Q000528:radiation effects*; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism* / Q000528:radiation effects*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D002839:Chromans; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid